All times are listed in CEST (Central European Summer Time)
17P - Treatment sequence for non-small cell lung cancer with brain oligometastases does not impact overall survival
- A. Kumar (New York, United States of America)
- A. Kumar (New York, United States of America)
- S. Kuhan (Boston, United States of America)
- A. Potter (Boston, United States of America)
- C. Mathey-Andrews (Boston, United States of America)
- H. G. Auchincloss (Boston, United States of America)
- D. Kozono (Boston, United States of America)
- C. Yang (Boston, United States of America)
Abstract
Background
For patients with non-small cell lung cancer (NSCLC) presenting with brain oligometastases, the optimal treatment sequence of thoracic and metastatic treatment is not well-established. This study sought to evaluate long-term survival of patients with NSCLC with brain oligometastases who received initial treatment of the primary site lung tumor versus brain metastases.
Methods
Patients with cT1-4, N0-3, M1b-c NSCLC with synchronous limited metastatic disease isolated to the brain who received systemic therapy with radical treatment (surgery, brain stereotactic radiosurgery, or lung radiation) to both the primary site and metastases in the National Cancer Database from 2010–2019 were included. Patients who received whole brain radiation therapy or palliative treatment were excluded. Long-term overall survival of patients who received initial treatment to the brain versus lung was evaluated using Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching, on 15 common prognostic variables including comorbidities, clinical T/N status, and the specific type of treatment to each site.
Results
Of the 1,044 patients diagnosed with NSCLC with brain oligometastases who met the study inclusion criteria, 893 (79.0%) received treatment of the brain metastases first, and 237 (21.0%) received treatment to the lung first. In unadjusted Kaplan-Meier analysis, overall survival was similar between patients who underwent initial treatment of brain metastases versus primary site. No significant difference in overall survival was found between the two groups after multivariable-adjusted Cox proportional hazards modeling (HR: 1.24, 95% CI: 0.91–1.70, p = 0.17). In a propensity score-matched analysis of 230 patients (115 in each arm), treatment sequence of brain metastases versus lung was not significantly associated with 5-year overall survival (Brain: 38.2% [95% CI: 27.5–34.4] vs Lung: 38.0% [95% CI: 29.9–44.7], p = 0.32).
Conclusions
The findings of this study suggest that for patients presenting with NSCLC with synchronous limited metastatic disease isolated to the brain who can tolerate aggressive treatment of the primary and metastatic sites, treatment sequence does not impact overall survival.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
18P - Stereotactic radiotherapy (SRT) in combination with aumolertinib to treat intracranial oligometastatic non-small cell lung cancer (NSCLC): An update of the phase II, prospective study
- J. Chen (Shanghai, China)
- J. Chen (Shanghai, China)
- H. Zhang (Shanghai, China)
- B. Wang (Shanghai, China)
- J. Wen (Shanghai, China)
- X. Xu (Shanghai, China)
- H. Li (Shanghai, China)
- M. Fan (Shanghai, China)
Abstract
Background
Aumolertinib is a tolerable third-generation EGFR-TKI that has CNS efficacy in patients with EGFR-mutant NSCLC. Stereotactic radiotherapy (SRT) is highly effective and less toxic for limited intracranial metastases. We aim to investigate the efficacy and safety of aumolertinib followed by SRT in patients with intracranial oligometastatic NSCLC.
Methods
Intracranial oligometastatic patients with EGFR sensitive mutations (EGFR-TKIs naive) were enrolled and received aumolertinib 110 mg daily until intracranial disease progression. Then SRT (32–40Gy total, 8Gy/f) was given to intracranial oligo-progression disease. After SRT the patients received continued aumolertinib if extracranial lesions were stable controlled. The primary endpoint was intracranial objective response rate (iORR). Secondary endpoints included intracranial progression-free survival (iPFS), intracranial duration of response (iDOR) according to RECIST 1.1, cerebral radiation necrosis rate (CRNR) and overall survival (OS). Safety was evaluated according to CTCAE v5.0.
Results
To January 6, 2023, a total of 35 patients were enrolled and 32 patients were assessed, and followed for 3 months to 16 months. All patients received 110 mg aumolertinib daily and received at least one independent imaging evaluation by a radiologist. After administration of aumolertinib, the best response of all patients in intracranial and extracranial lesions was partial response (PR), with an iORR of 100%. At data cut-off, one patient developed intracranial primary lesion progression at 12 months after aumolertinib treatment but stable in extracranial lesions. SRT treatment was given to this patient. No grade ≥3 adverse events occurred after continued aumolertinib. The most common adverse reactions were rash and abnormal liver enzymes.
Conclusions
This report showed pronounced intracranial objective response benefit with aumolertinib in patients with intracranial oligometastatic disease followed by SRT after intracranial oligo-progression and no new safety signals. Aumolertinib has promising efficacy and good tolerability in intracranial oligometastatic EGFR mutated NSCLC.
Clinical trial identification
NCT04519983.
Legal entity responsible for the study
The authors.
Funding
Hansoh Pharmaceutical Group Company Limited.
Disclosure
H. Zhang: Financial Interests, Personal, Sponsor/Funding: Hansoh Pharma. All other authors have declared no conflicts of interest.
19P - Mortality among EGFR-mutated advanced NSCLC patients after frontline osimertinib treatment: A real-world, US attrition analysis
- N. Girard (Paris, France)
- N. Girard (Paris, France)
- Y. Ohe (Tokyo, Japan)
- T. Kim (Seoul, Korea, Republic of)
- L. Demirdjian (Spring House, United States of America)
- A. B. Bourla (Spring House, United States of America)
- A. Abdul Sultan (Raritan, United States of America)
- P. Mahadevia (Spring House, United States of America)
- J. M. Bauml (Spring House, United States of America)
- J. Sabari (New York, United States of America)
Abstract
Background
The recommended frontline therapy for patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC is osimertinib (osi), a 3rd‐generation (gen) EGFR tyrosine kinase inhibitor (TKI); however, most will develop resistance. Approximately 28% of frontline pts treated with a 1st/2nd-gen EGFR TKI die before receiving a 2nd line of therapy (LOT) (Nieva Drugs Real World Outcomes 2022; 9:333–345). This analysis estimated mortality in EGFRm NSCLC after starting frontline osi and before 2nd LOT to determine if there is an improvement to historical rates.
Methods
Data from the ConcertAI (Cambridge, MA) Patient360 NSCLC database (>100 geographically dispersed community US oncology practices) were analyzed descriptively. Included pts were diagnosed with advanced NSCLC between 1 Jan 2018 and 16 Aug 2022, had confirmed EGFR exon 19 deletions (ex19del) or exon 21 L858R mutations, and received osi (primary analysis) or 1st/2nd-gen EGFR TKI (ie, afatinib, erlotinib, or gefitinib) as frontline monotherapy.
Results
In the ConcertAI Patient360 database, 1,135 pts had confirmed EGFR ex19del or L858R; of which 467 (41%) received osi as frontline monotherapy. Among this frontline osi population, 119 (25%) died before receiving a subsequent LOT. Documented start of a 2nd LOT was observed in 133 (28%) of frontline osi-treated pts. The remaining 215 (46%) did not have documented start of a 2nd LOT, which could be due to ongoing frontline use. A similar proportion of frontline 1st/2nd-gen EGFR TKI pts died prior to a 2nd LOT (20%;
Patient attrition
| Of patients receiving frontline, n (%) | Osimertinib (n = 467) | 1st or 2nd-gen EGFR TKI (n = 61) |
|---|---|---|
| Median follow-up | 2.1 years | 2.9 years |
| Died during frontline | 119 (25) | 12 (20) |
| No documented start of 2nd LOT | 215 (46) | 8 (13) |
| Started 2nd LOT | 133 (28) | 41 (67) |
Cross-cohort analysis was not conducted, and therefore, confounding factors cannot be ruled out.
Conclusions
The proportion of EGFRm NSCLC pts dying while on frontline osi (25%) remains high, demonstrating many never get to a 2nd LOT. Further optimization of frontline therapy is needed to improve patient outcomes.
Editorial acknowledgement
Medical writing support was provided by Lumanity Communications, Inc.
Legal entity responsible for the study
The authors.
Funding
Janssen.
Disclosure
N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Personal, Other, Family member is an employee: AstraZeneca. N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Eli Lilly, MSD, Pfizer, Roche, Takeda. Y. Ohe: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, ONO, BMS, Eli Lilly, Boehringer Ingelheim, Takeda, MSD, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Celltrion, Amgen, Nippon Kayaku, Takeda, Pfizer, ONO, Janssen, AnHeart Therapeutics Inc; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Eli Lilly, Janssen, Amgen; Financial Interests, Personal and Institutional, Invited Speaker: Takeda, ONO; Non-Financial Interests, Personal, Leadership Role: JSMO, JLCS, JCOG; Non-Financial Interests, Personal, Member: ASCO. T.M. Kim: Financial Interests, Personal, Advisory Role: Honoraria for lectures from AstraZeneca, IMBDx, Inc., Takeda, and Yuhan; Financial Interests, Personal, Other: AstraZeneca, Janssen, Regeneron, Samsung. L. Demirdjian: Financial Interests, Personal, Full or part-time Employment: Janssen. A.B. Bourla: Financial Interests, Personal, Full or part-time Employment: Flatiron Health/ Roche Group, Janssen R & D. A. Abdul Sultan: Financial Interests, Personal, Full or part-time Employment: Janssen. P. Mahadevia: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Mirati Therapeutics.
20P - Efficacy and safety of AZD3759 in previously untreated EGFR-mutant non-small cell lung cancer with central nervous system metastases in a multi-center, phase II umbrella trial (CTONG1702)
- S. M. Liu (Guangzhou, China)
- S. M. Liu (Guangzhou, China)
- Q. Zhou (Guangzhou, China)
- C. Lu (Guangzhou, China)
- J. Deng (Guangzhou, China)
- Z. Wang (Guangzhou, China)
- Y. Li (Guangzhou, China)
- M. Zheng (Guangzhou, China)
- B. Xu (Guangzhou, China)
- X. Dong (Wuhan, China)
- Y. Du (Hefei, China)
- J. Cui (Changchun, China)
- Q. Chu (Wuhan, China)
- X. Bai (Guangzhou, China)
- Y. Sun (Guangzhou, China)
- A. Li (Guangzhou, China)
- C. Xu (Guangzhou, China)
- B. Wang (Guangzhou, China)
- H. Chen (Guangzhou, China)
- J. Yang (Guangzhou, China)
- Y. Wu (Guangzhou, China)
Abstract
Background
Non-small cell lung cancer (NSCLC) had poor prognosis in patients with central nervous system (CNS) metastases. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has changed the treatment paradigm of advanced EGFR-mutant patients. However, limited benefit has been observed in patients with EGFR mutation and CNS metastases with available EGFR-TKIs.
Methods
We initiated an umbrella trial (CTONG1702), in the 8th arm to access the efficacy and safety of AZD3759, an EGFR-TKI with high capability to penetrate the blood-brain barrier, in untreated EGFR-mutant NSCLC with brain or leptomeningeal metastases. Patients received AZD3759 200 mg or 300 mg BID. The primary objective was objective response rate (ORR). To determine whether AZD3759 has sufficient activity, we used Simon's minimax two-stage to calculate sample size.
Results
30 patients were enrolled and received AZD3759 at 200 mg (n = 15) or 300 mg (n = 15) BID. As of June 30 2022, the median follow-up is 31.6 months. The ORR was 70% (21/30), which was 80% (12/30) in 200 mg group and 60% (9/30) in 300 mg group, respectively. The median progression-free survival (PFS) was 13.9 months and median overall survival (OS) was 37.0 months. The survival benefit was greater in 200 mg than in 300 mg groups. Treatment-related adverse events with grade ≥3 occurred in 21 (70%) patients, which was (60.0%) in 200 mg group and 13 (86.7%) in 300 mg group, respectively. The most common adverse events are rash and diarrhea. Of 16 patients who had tumor or liquid biopsy to analyze acquired resistant mechanism, 10 (62.5%) developed EGFR T790M. Of 30 enrolled patients, 13 received osimertinib as 2nd-line therapy.
Conclusions
This is the first report to present phase II study outcome of AZD3759 with promising efficacy and tolerable safety in the selected population with CNS metastases. We suggested 200 mg BID was a better dose with superior response and lower toxicity. EGFR T790M was the most common resistant mutation, and these patients still have the opportunity to receive osimertinib after progression of AZD3759.
Clinical trial identification
NCT03574402.
Legal entity responsible for the study
Chinese Thoracic Oncology Group (CTONG).
Funding
This work was funded by National Natural Science Foundation of China (82202997, Si-Yang Maggie Liu), Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (2017B030314120, Yi-Long Wu), Guangdong Provincial People's Hospital Scientific Research Funds for Leading Medical Talents in Guangdong Province (KJ012019426, Yi-Long Wu), and the High-Level Hospital Construction Project (DFJH201810, Qing Zhou).
Disclosure
Q. Zhou: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, Sanofi. Y. Wu: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Eli Lilly, Boehringer Ingelheim, Sanofi, MSD, BMS. All other authors have declared no conflicts of interest.
21P - Bevacizumab plus atezolizumab and chemotherapy in NSCLC harbouring EGFR mutation previously treated with EGFR tyrosine kinase inhibitor: The BACH-NET study
- G. Pasello (Padova, Italy)
- G. Pasello (Padova, Italy)
- M. Lorenzi (Padova, Italy)
- G. Crivellaro (Padova, Italy)
- E. Capelletto (Orbassano, Italy)
- S. Butticè (Orbassano, Italy)
- F. Perrone (Parma, Italy)
- M. Tiseo (Parma, Italy)
- V. Scotti (Firenze, Italy)
- V. Polo (Treviso, Italy)
- A. Favaretto (Treviso, Italy)
- M. Montrone (Bari, Italy)
- R. Berardi (Ancona, Italy)
- F. Zustovich (Belluno, Italy)
- L. Toschi (Rozzano, Italy)
- A. Bearz (Aviano, Italy)
- M. Milella (Verona, Italy)
- S. Frega (Padova, Italy)
- L. Bonanno (Padova, Italy)
- V. Guarneri (Padova, Italy)
Abstract
Background
Atezolizumab (A)/Bevacizumab(B)/Carboplatin/Paclitaxel (CP) has been proposed as a second-line option in EGFR mutant (EGFRm) non-small lung cancer (NSCLC) patients (pts) progressing to EGFR tyrosine kinase inhibitors (TKIs) without druggable resistance targets on the basis of an exploratory analysis of the phase III trial IMpower150. A therapeutic named use program has been open in Italy (June 2019-July 2020), although this regimen has not been approved. A real-world study has been designed in order to acquire more solid data about its feasibility.
Methods
This is a retrospective-prospective observational multicenter study with the primary aim to assess the feasibility of ABCP (rate of ineligible patients/potentially candidates) according to clinicians’ selection criteria in the real-world practice of 11 Italian centres. Secondary endpoints are overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR), duration of response (DoR), time to treatment failure and discontinuation (TTF and TTD), safety and quality of life (QOL).
Results
We report preliminary data from 80 EGFRm NSCLC pts progressing to TKIs. Overall, twenty-two received the ABCP regimen, with an ineligibility rate of 80%, mostly because of poor performance status (PS) and age. After a median follow-up of 14.2 months (mos), median TTD and TTF of 8.0 and 8.7 mos, respectively, were observed. The RR was 32% and DCR was 82%, with a median DoR of 3.9 mos. The median PFS was 5.7 mos and the OS was 16.2 mos. Adverse events (AEs) occurred in 15 (68%) patients: 6 (27%) G3/G4, 1 (5%) G5 (pneumonia). The most frequent AEs were: fatigue (36.4%), hypertension (18.2%), non-febrile neutropenia (18.2%). The QOL assessment through EORTC, QLQ-C30 e QLQ-LC13 scales, showed a worsening of the global health, the person's ability and the symptoms after the first or second cycle of treatment.
Conclusions
This observational study included a more representative sample of patients of the clinical practice, (poor PS; comorbidities). The high rate of ineligibility confirms this combination regimen as not feasible for most patient. Median OS, PFS and the incidence of AEs are lower than in the IMpower150 trial.
Legal entity responsible for the study
University of Padova.
Funding
University of Padova and Istituto Oncologico Veneto IRCCS.
Disclosure
All authors have declared no conflicts of interest.
22P - Adding anlotinib in gradual or local progression on first-line EGFR-TKIs for advanced non-small cell lung cancer: A single-arm, multicenter, phase II trial
- H. Chen (Guangzhou, China)
- H. Chen (Guangzhou, China)
- Y. Hu (Wuhan, China)
- Y. Fan (Hangzhou, China)
- G. Wu (Meizhou, China)
- S. Cang (Zhengzhou, China)
- Y. Yang (Chendu, China)
- N. Yang (Changsha, China)
- R. Ma (Shenyang, China)
- G. Jing (Huhhot, China)
- A. Liu (Nanchang, China)
- X. Xu (Wuhan, China)
- S. Tang (Neijiang, China)
- Y. Cheng (Changchun, China)
- Y. Yu (Harbin, China)
- Y. Wu (Guangzhou, China)
Abstract
Background
Anlotinib plus EGFR-TKIs continuation was a potential treatment strategy in selected advanced non-small cell lung cancer (NSCLC) after disease progression in first-line EGFR-TKIs. This study aimed to evaluate the efficacy and safety of combined EGFR-TKIs and anlotinib.
Methods
The trial aimed to enroll 120 patients after gradual or local progression in EGFR-TKIs treatment. All patients were treated with oral anlotinib 12 mg daily for 14 days every three weeks until disease progression or intolerable toxicity. The primary end-point was progression-free survival (PFS). The secondary end-points were 6 months and 12 months PFS rate, Overall response rate (ORR), disease control rate (DCR), overall survival (OS) and safety.
Results
From July 08, 2019 to December 15, 2022 the enrollment was completed, including 109 patients with gradual progression. Up to December 31, 2022, 114 patients were available for efficacy assessment (105 patients had confirmed evaluation). Median PFS of combined anlotinib and EGFR-TKIs treatment was 9.2 months (95% CI, 6.6–11.6). Confirmed ORR was 5.7% and DCR was 92.4%. The PFS rate at 6 and 12 months was 66.3% and 36.7% respectively. Safety assessment was available in 116 patients, 94% (109/116) patients were reported treatment related adverse events (TRAEs). The incidence of grade 3 or 4 TRAEs was 36.2% (42/116) and the treatment-related serious adverse event (SAE) was 7.8% (9/116). The common TRAEs were diarrhea (47.4%), hypertension (42.2%), proteinuria (39.7%), and hypertriglyceridemia (24.1%). 22.4% (26/116) of patients experienced anlotinib dose reduction.
Conclusions
EGFR-TKIs plus anlotinib demonstrated meaningful clinical control in advanced NSCLC after gradual or local progression in first-line EGFR-TKIs. And the toxicity was clinically manageable.
Clinical trial identification
NCT04007835.
Legal entity responsible for the study
Guangdong Association of Clinical Trials.
Funding
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.
23P - Impact of PDL1 expression on outcomes of patients with EGFR mutant NSCLC treated with EGFR TKIs: First results of the POET study
- L. Belluomini (Verona, Italy)
- L. Belluomini (Verona, Italy)
- M. Ferrara (Rome, Italy)
- M. Sposito (Verona, Italy)
- A. Vitale (Rome, Italy)
- J. Insolda (Verona, Italy)
- E. Vita (Rome, Italy)
- D. Giannarelli (Rome, Italy)
- A. Stefani (Rome, Italy)
- M. Milella (Verona, Italy)
- E. Bria (Rome, Italy)
- S. Pilotto (Verona, Italy)
Abstract
Background
In EGFR mutant NSCLC, acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) inevitably occurs. To date, inconclusive results have been published or presented regarding the predictive/prognostic role of PDL1 expression in EGFR mutant NSCLC treated with TKIs.
Methods
A retrospective analysis of patients treated with first (Erlotinib/Gefitinib), second (Afatinib) and third generation (Osimertinib) EGFR-TKIs was conducted. The main objective was to evaluate the potential correlation between levels of PDL1 expression and anti-EGFR treatment efficacy in terms of overall survival (OS) and progression-free-survival (PFS).
Results
Data from 171 patients (median age 69.0 years) who received EGFR TKIs were gathered. The most common EGFR alteration was ex19del (52.6%). 26 patients (15.2%) showed high PDL1 expression (≥50%). 105 patients (61.4%) were treated with Osimertinib, while 22.2%, 12.3% and 4.1% were treated with Gefitinib, Afatinib and Erlotinib, respectively. In the overall population, the objective response rate was 61%, mPFS 19.1 months (15.1–23.1) and 2-year OS 61.5%. Results of multivariate analysis are reported in the
| Univariate HR (95% CI) | Multivariate HR (95% CI) | |
|---|---|---|
| ECOG PS | P < 0.0001 | P = 0.002 |
| 0 | 1.00 | 1.00 |
| 1 | 1.33 (0.80–2.21) | 1.60 (0.95–2.72) |
| 2–3 | 5.09 (2.70–9.60) | 3.73 (1.78–7.82) |
| PDL1 | P = 0.03 | P = 0.073 |
| <=49% | 1.00 | 1.00 |
| >=50% | 1.87 (1.06–3.29) | 1.71 (0.95–3.08) |
| Mutation | p = 0.11 | |
| Esone 19 | 1.00 | |
| Esone21 | 1.24 (0.77–2.00) | |
| Number of met sites | P = 0.40 | |
| 1 | 1.00 | |
| 2 | 1.69 (0.71–4.03) | |
| >=3 | 1.72 (0.78–3.79) | |
| Surgery | P = 0.03 | P = 0.095 |
| No | 1.00 | 1.00 |
| Yes | 0.46 (0.23–0.93) | 0.54 (0.26–1.12) |
| TKIs | P = 0.006 | P = 0.001 |
| Gefitinib/Erlotinib | 1.00 | 1.00 |
| Afatinib | 0.62 (0.31–1.26) | 0.48 (0.22–1.06) |
| Osimertinib | 0.45 (0.27–0.73) | 0.36 (0.21–0.61) |
| First-line | P < 0.0001 | P = 0.08 |
| No | 1.00 | 1.00 |
| Yes | 0.14 (0.06–0.35) | 0.39 (0.13–1.12) |
Conclusions
Our study supports the survival benefit of Osimertinib compared to first/second generation TKIs, regardless of PDL1 expression. A larger data collection is ongoing and updated results will be presented at the Conference.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
E. Bria: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, BMS, MSD, Eli Lilly, Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche. S. Pilotto: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, AstraZeneca, Merck & Co., Roche, Amgen, Novartis; Financial Interests, Personal, Advisory Board: Merck & Co., Amgen, AstraZeneca, Novartis; Financial Interests, Personal, Expert Testimony: Takeda; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Roche. All other authors have declared no conflicts of interest.
24P - Efficacy and safety of 1st generation EGFR TKI retreatment in EGFR mutation-positive, T790M-negative patients previously treated with 1st or 2nd generation EGFR TKI and cytotoxic chemotherapy
- S. Lee (Seoul, Korea, Republic of)
- S. Lee (Seoul, Korea, Republic of)
- J. Choi (Seoul, Korea, Republic of)
- J. Lee (Seoul, Korea, Republic of)
- C. Choi (Seoul, Korea, Republic of)
- I. Kim (Seoul, Korea, Republic of)
- K. Lee (Seoul, Korea, Republic of)
- J. Lee (Daejeon, Korea, Republic of)
- S. Jang (Anyang, Korea, Republic of)
- S. Yoon (Yangsan, Korea, Republic of)
- I. Oh (Hwasun, Korea, Republic of)
- S. Lee (Seoul, Korea, Republic of)
- E. Kim (Seoul, Korea, Republic of)
Abstract
Background
Although osimertinib has been approved as first-line therapy, 1st or 2nd generation EGFR TKIs are still being used as first-line therapy. Although T790M acquired resistance occurs 30 to 40% after the treatment of the 1st- or 2nd-generation EGFR TKIs, most cases of T790M mutation-negative patients undergo cytotoxic chemotherapy or other supportive treatment. There are several reports that EGFR TKI re-administration may be helpful in T790M-negative patients. We did prospectively undergo EGFR TKIs retreatment trial as a third or later line treatment.
Methods
The enrolled patients were resistant to 1st or 2nd generation EGFR-TKI as a 1st-line treatment and then treated with chemotherapy for more than 4 cycles because of T790M-negative at 2nd biopsy. The primary endpoint was objective response rate (RR), and the secondary endpoints were progression free survival (PFS), overall survival (OS), and safety.
Results
In total, 63 patients retreated with gefitinib (n = 34) or erlotinib (n = 29) after the progression of 2nd or more line chemotherapy. The median age was 65. The best RR and disease control rate were 14 and 51%, respectively. The median duration of treatment was 65 days (gefitinib 56 days vs. erlotinib 90 days). The median PFS was 2.8 months (gefitinib 1.8 vs. erlotinib 3.5 months), median OS was 8.5 months (gefitinib 8.3 vs. erlotinib 9.0 months). The development rate of T790M after the retreatment of EGFR TKIs was 32% (20/63). Acquired T790M mutation developed in 13 of 20 patients (65%) who had exon 19 del. The median duration from the start of EGFR TKI retreatment to the date of the T790M mutation development was 5.2 months. There was a statistical difference in OS between T790M-negative and induced patients (5.4 vs. 28.9 months, P < 0.001). The most common adverse events were diarrhea and skin toxicities.
Conclusions
Retreatment with EGFR-TKIs can be considered an option after the failure of chemotherapy for patients who were previously controlled by EGFR-TKI. The 1st generation EGFR TKIs retreatment may induce T790M mutation (32%) in patients who had not previously T790M mutation, leading to 3rd generation EGFR TKI sequential treatment and eventually prolong OS.
Clinical trial identification
NCT03382795.
Legal entity responsible for the study
The authors.
Funding
Chong Kun Dang Pharmaceutical Company.
Disclosure
All authors have declared no conflicts of interest.
25P - Furmonertinib plus icotinib for first-line treatment of EGFR-mutated non-small cell lung cancer
- H. Chen (Zhanjiang, China)
- H. Chen (Zhanjiang, China)
- M. Lin (Zhanjiang, China)
- J. Jiang (Zhanjiang, China)
- M. Liu (Zhanjiang, China)
- Z. Lai (Zhanjiang, China)
- Y. Luo (Zhanjiang, China)
- H. Ye (Zhanjiang, China)
- H. Chen (Zhanjiang, China)
- Z. Yang (Zhanjiang, China)
Abstract
Background
Furmonertinib is a highly brain-penetrant, pan epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with activity against EGFR classical, T790M resistant and Ex20ins mutations. Icotinib is a first-generation EGFR TKI widely used in China and may overcome the resistance of furmonertinib due to EGFR C797S mutation. Furmonertinib plus icotinib may delay emergence of acquired resistance in the first-line setting.
Methods
This ongoing phase II study enrolled untreated advanced non-small cell lung cancer (NSCLC) patients with Ex19Del/L858R/Ex20ins mutation. Patients with stable central nervous system (CNS) metastases were allowed to enroll. The regimen consisted of furmonertinib (80 mg p.o, qd) and icotinib (125 mg p.o, tid). The primary endpoint was PFS. Secondary endpoints were ORR, DCR, OS, and safety.
Results
40 patients were planned to be enrolled in this study. As of Nov 30 2022, 18 patients were enrolled and received study treatment. Patients’ baseline characteristics included median age 61.5-years (range 43–82), female 55.6%, ECOG PS 0/1/2 0/88.9%/11.1%, Ex19Del/L858R/Ex20ins 55.6%/38.9%/5.6%, CNS metastases 83.3%. Median follow-up was 230 days and the median PFS was not yet reached. The confirmed ORR assessed by investigator based on RECIST 1.1 was 88.9% (16 PR), DCR was 100% (16 PR, 2 SD). In patients with CNS metastasis the ORR was 86.7%, and the DCR was 100%. Tumor shrinkage was observed in all patients with a median best percent change of −34.3% (range: −76.1, −27.1). The most commonly observed treatment-emergent adverse events (TEAEs) included diarrhea, liver enzyme elevation and rash. One patient experienced a grade 3 TEAE due to diarrhea, and no other grade≥3 TEAE was observed.
Conclusions
Furmonertinib plus icotinib as first-line treatment showed encouraging antitumor activity and well tolerated safety profile in EGFR-mutated NSCLC. The observed AEs were consistent with those previously reported. This study is still ongoing and more results will be evaluated in the future, which may contribute to definite the role of dual EGFR TKI therapy in first-line setting.
Clinical trial identification
ChiCTR2200060151.
Legal entity responsible for the study
The authors.
Funding
Shanghai Allist Pharmaceuticals Co., Ltd, Shanghai, China.
Disclosure
All authors have declared no conflicts of interest.
26P - Real-world use of tyrosine kinase inhibitors (TKI) in epidermal growth factor receptor mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) in nine countries
- J. Samol (Singapore, Singapore)
- J. Samol (Singapore, Singapore)
- I. Demedts (Roselare, Belgium)
- M. Erman (Ankara, Turkey)
- V. Kozlov (Novosibirsk, Russian Federation)
- J. Minatta (Buenos Aires, Argentina)
- F. V. Moiseenko (Saint-Petersburg, Russian Federation)
- M. S. Paats (Rotterdam, Netherlands)
- S. Rajappa (Hyderabad, India)
- T. Bailey (Macclesfield, United Kingdom)
- H. Wallis (Bollington, United Kingdom)
- M. Madondo (Cambridge, United Kingdom)
- D. Kahangire (Cambridge, United Kingdom)
- M. Zukin (Rio de Janeiro, Brazil)
Abstract
Background
EGFR mutations occur in 10–50% of NSCLC patients globally. EGFR testing is recommended for NSCLC, with EGFR-TKIs recommended as the optimal first-line (1L) treatment for patients with advanced EGFRm NSCLC. This study investigated EGFR testing turnaround time and real-world treatment patterns in patients with advanced EGFRm NSCLC in nine countries.
Methods
A retrospective chart review was conducted from June to September 2021 in Argentina, Belgium, Brazil, India, Netherlands, Russia, Singapore, Switzerland, and Turkey. Overall, 947 case report forms were collected for patients who presented with advanced/metastatic (stage IIIB/C/IV) NSCLC who received a positive first EGFR test result between 01 April 2017–31 March 2018 (index date). Data on demographics, clinical characteristics, EGFR testing, and treatment patterns were abstracted from diagnosis until June 2020 (or death).
Results
Demographics and clinical characteristics are described in the
| Overall n = 947 | |
|---|---|
| Median age at diagnosis, years (range) | 61.4 (20.0–90.0) |
| Sex, n (%) | |
| Male | 500 (53%) |
| Female | 447 (47%) |
| Smoking status, n (%) | |
| Current smoker | 141 (15%) |
| Ex-smoker | 291 (31%) |
| Never smoked | 393 (41%) |
| EGFR Test performed as single gene test or as part of a panel, n (%) | |
| Single gene test | 606 (64%) |
| Part of a panel | 341 (36%) |
| EGFR Mutation type recorded since diagnosis (most commonly reported), n (%) | |
| Exon 19 deletion | 346 (37%) |
| L858R | 310 (33%) |
| T790M | 115 (12%) |
Conclusions
Median EGFR test turnaround time was longer than the 10 working days recommended by guidelines; suggestive of the need to improve EGFR testing practices to ensure timely initiation of targeted therapy. As this study included dates up until 2020, testing practices may have improved since study end. For patients treated with an EGFR-TKI as 1L therapy, TTFST in this real-world study was favourable. However, 31% of EGFRm patients did not receive a 1L EGFR-TKI. The results suggest an unmet need to optimise treatment strategies for patients with advanced EGFRm NSCLC.
Editorial acknowledgement
We would like to acknowledge Victoria Davis from Adelphi Real World for her medical writing support.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
I. Demedts: Financial Interests, Institutional, Advisory Board, ID declares consultancy fee for advisory board: AstraZeneca. M. Erman: Financial Interests, Institutional, Advisory Board, ME declares taking part in presentations and advisory boards for listed companies: Novartis, Pfizer, Roche, Astellas, MSD, Deva, AstraZeneca, Janssen, Gen, Nobel, Eczacibasi, BMS, Takeda. J.N. Minatta: Financial Interests, Institutional, Funding, Author was an investigator in clinical trials sponsored by companies listed: AstraZeneca, BMS, Janssen, Roche, MSD, GSK; Financial Interests, Personal, Advisory Board, Consulting/ Advisory Board, Educational: MSD, Pfizer, Takeda, Amgen. F.V. Moiseenko: Financial Interests, Personal, Other, FM declares personal fees from listed companies: Pfizer, AstraZeneca, Takeda, Biocad, Novartis, MSD, Roche, BMS, Eli Lilly; Non-Financial Interests, Personal, Other, FM declares non-financial support from listed companies: AstraZeneca, Biocad, Boehringer Ingelheim. T. Bailey: Financial Interests, Institutional, Other, TB is an employee of Adelphi Real World, who have received funding from AstraZeneca for this work: AstraZeneca. H. Wallis: Financial Interests, Institutional, Other, HW is an employee of Adelphi Real World, who have received funding from AstraZeneca for this work: AstraZeneca. M. Madondo: Financial Interests, Institutional, Other, MM is an employee of AstraZeneca: AstraZeneca. D. Kahangire: Financial Interests, Institutional, Other, DK is an employee of AstraZeneca: AstraZeneca. All other authors have declared no conflicts of interest.
27P - Amivantamab versus alternative real-world anti-cancer therapies in patients with advanced non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations in the US and Europe
- N. Girard (Paris, France)
- N. Girard (Paris, France)
- J. Wolf (Cologne, Germany)
- T. Kim (Seoul, Korea, Republic of)
- N. Leighl (Toronto, Canada)
- C. Knott (London, United Kingdom)
- T. Li (Raritan, United States of America)
- J. Cabrieto (Raritan, United States of America)
- J. Diels (Beerse, Belgium)
- J. Sermon (Beerse, Belgium)
- P. Mahadevia (Spring House, United States of America)
- C. A. Schioppa (Beerse, Belgium)
- J. Sabari (New York, United States of America)
Abstract
Background
Amivantamab was the first approved therapy for advanced/metastatic NSCLC harboring EGFR exon 20 insertion mutations (Ex20ins) who progressed on platinum chemotherapy (CT). Since Ex20ins is uncommon, it may be confused with activating EGFR mutations resulting in treatment with limited benefit. This study estimates the relative effectiveness of amivantamab versus alternative anti-cancer treatments used in real-world settings for NSCLC with Ex20ins.
Methods
Data from the single-arm CHRYSALIS trial were compared to an external cohort of patients derived from six US and European real-world data sources that met the CHRYSALIS Cohort D+ eligibility criteria. Amivantamab was compared to EGFR TKIs including osimertinib, immunotherapy, non-platinum CT, VEGFi + CT, and others. Patient-level data were used to adjust for differences in prognostic factors using inverse probability weighting (average treatment effect among the treated). Binary and time-to-event endpoints were analyzed using weighted logistic regression and proportional hazards regression, respectively.
Results
After adjustment, baseline characteristics between the two cohorts were balanced. For all individual treatment class comparisons, results were consistently in favor of amivantamab in overall survival (OS), progression free survival (PFS), time to next treatment (TTNT), and overall response rate by investigator (ORR-INV) (see
| Treatment | Adjusted Hazard Ratio (95% CI) for amivantamab vs. other treatment | ||||
|---|---|---|---|---|---|
| N | ORR-INV | OS | PFS-INV | TTNT | |
| Amivantamab | 114 | 36.8% | – | – | – |
| All EGFR TKIs | 69 | 5.3% | 0.46 (0.30, 0.72) | 0.51 (0.34, 0.76) | 0.38 (0.26, 0.55) |
| Osimertinib subgroup | 22 | 0.0% | 0.37 (0.19, 0.73) | 0.67 (0.33, 1.37)^ | 0.55 (0.31, 0.98) |
| Immunotherapy | 91 | 13.2% | 0.40 (0.27, 0.60) | 0.42 (0.31, 0.58) | 0.41 (0.29, 0.57) |
| Non-platinum chemotherapy | 87 | 18.1% | 0.45 (0.29, 0.70) | 0.52 (0.36, 0.76) | 0.36 (0.25, 0.53) |
| VEGFi + chemotherapy | 57 | 21.4%^ | 0.54 (0.34, 0.85) | 0.60 (0.42, 0.87) | 0.53 (0.35, 0.79) |
| Other | 79 | 27.2% | 0.58 (0.36, 0.92) | 0.61 (0.43, 0.87) | 0.51 (0.35, 0.75) |
No statistically significant difference vs. amivantamab; all other values significant.
Conclusions
Based on this adjusted treatment comparison, amivantamab provides significant benefits compared to alternative therapies used in real world practice. Education on appropriate treatment choice is important to advance quality of cancer care.
Editorial acknowledgement
The authors acknowledge Heather Burnett of Evidera, a ThermoFisher company, for medical writing and ediotrial assistance based on the author's input and direction.
Legal entity responsible for the study
The authors.
Funding
Janssen.
Disclosure
N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Personal, Other, Family member is an employee: AstraZeneca. J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Ignyta, Janssen, Eli Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. T.M. Kim: Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Regeneron, Takeda; Financial Interests, Personal, Invited Speaker: AstraZeneca, IMBDx, Inc., Takeda, Yuhan; Financial Interests, Personal, Advisory Role: AstraZeneca, Janssen, Regeneron, Samsung Bioepis, Takeda, Yuhan; Financial Interests, Personal, Research Grant: AstraZeneca-KHIDI; Non-Financial Interests, Institutional, Writing Engagements: AbbVie, AstraZeneca, Bayer, Black Diamond Therapeutics, Blueprint Medicines, Boryung, Bristol Myers Squibb, Celgene, F. Hoffman-La Roche Ltd/Genentech, Inc., Hanmi, Janssen, Novartis, Regeneron, Sanofi; Non-Financial Interests, Institutional, Invited Speaker: Takeda, Yuhan. N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Eli Lilly, MSD, Pfizer, Roche, Takeda. T. Li: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. J. Cabrieto: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. J. Diels: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. J. Sermon: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. P. Mahadevia: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. C.A. Schioppa: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. J. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Mirati Therapeutics. All other authors have declared no conflicts of interest.
28P - Generation and validation of a predictive model using pretreatment clinical factors for estimating survival and T790M mutation in EGFR-mutated non-small cell lung cancer in Taiwan
- C. Lin (Tainan City, Taiwan)
- C. Lin (Tainan City, Taiwan)
- Y. Chou (Tainan City, Taiwan)
- C. Lin (Tainan City, Taiwan)
- C. Wu (Taoyuan City, Taiwan)
- C. Yang (Taoyuan City, Taiwan)
- J. Chang (Taipei City, Taiwan)
Abstract
Background
Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have been the standard treatment for advanced EGFR-Mutated NSCLC, the generation and validation of a comprehensive platform in predicting survival of these patients remain rare.
Methods
From October 2010 to 2021, we collected potential prognostic factors from advanced stage NSCLC patients receiving EGFR-TKI treatment at National Chen-Kung University, Tainan, Taiwan (NCKUH). Using univariate and multivariate analyses, we identify potential prognostic factors and create a nomogram for risk stratification accordingly. Then we validated the platform in another cohort from Chang Gung Memorial Hospital.
Results
Records of 761 EGFR-Mutated NSCLC patients from NCKUH were retrospectively reviewed. Using univariate analysis, we identified 8 prognostic factors including sex, ECOG status, morphology, mutation, stage, the choice of EGFR-TKIs, and metastasis to liver, brain and multivariate analysis confirmed their independent significance. We established a nomogram based on these factors and successfully classified patients into different risk groups with different survival. This nomogram can be used to predict the possibility of 6-,9-, and 12-month PFS and stratify patients into different risk groups for PFS and OS. In addition, patients with shorter PFS predicted by the nomogram had significantly higher incidence of acquired T790M mutation upon disease progression, which implied the early emergence of T790M might be predicted by this nomogram. We then successful validated the risk score in another cohort including 751 EGFR-Mutated NSCLC patients from Chang-Gung Memorial Hospital. The calibration curves for the probability of survival at 6, 9, and 12 months after EGFR-TKI use revealed a good concordance between the nomogram prediction and actual observation. Moreover, the calibration curves of these two cohorts showed similar pattern.
Conclusions
Our risk stratification can provide additional information to clinicians to evaluate the prognosis and the chance of sequential therapy in patients with EGFR-Mutated NSCLC patients who received targeted therapy.
Legal entity responsible for the study
The authors.
Funding
National Science and Technology Council (110-2314-B-006 -098 -MY3,109-2314-B-006-083 and MOST 108-2314-B-006-092-MY2.
Disclosure
All authors have declared no conflicts of interest.
29P - Real-world data of atezolizumab in combination with bevacizumab, and platinum-based chemotherapy for EGFR-mutant metastatic non-small cell lung cancer patients after failure of EGFR tyrosine kinase inhibitors
- S. Wu (Taipei, Taiwan)
- S. Wu (Taipei, Taiwan)
- Y. Huang (Taipei City, Taiwan)
- C. Ho (Taipei, Taiwan)
- W. Liao (Taipei, Taiwan)
- T. Tsai (Taipei, Taiwan)
- J. Yang (Taipei City, Taiwan)
- J. Shih (Taipei City, Taiwan)
Abstract
Background
IMpower150 study showed that the combination of immune chemotherapy plus bevacizumab provided a favorable efficacy for patients with non-squamous lung cancer harboring EGFR mutations. Although its effectiveness has been approved, little is known about the clinical outcome of the combination therapy in routine practice, especially for the Asian population with high EGFR mutation incidence. The current study aimed to explore the clinical efficacy and prognosis of combinational treatment with atezolizumab, bevacizumab, and platinum-based chemotherapy in patients with EGFR-mutated lung cancer who progressed with standard EGFR-targeted therapies.
Methods
From April 2019 to June 2022, we retrospectively collected patient-level data on atezolizumab-bevacizumab-chemotherapy combination treatment in NSCLC patients with EGFR mutations after the failure of EGFR TKIs at the National Taiwan University Hospital. The patient's clinical characteristics and treatment outcomes were recorded.
Results
We collected 36 patients, including 28 females and 35 non-smokers. The median age was 59.5 (range 40.4–81.3) years. EGFR mutation types included 13 deletion in exon19, 19 L858R, and 4 uncommon types. Before the combination therapy, 24 (66.7%) patients and 11 (30.6%) patients have taken osimertinib and anti-angiogenesis, respectively. PD-L1 expression was ≧ 1% in 19 (52.8%) patients. The treatment outcomes included a response rate of 44.4% (16 of 36), median progression-free survival (mPFS) of 7.8 months, and median overall survival of 16.7 months. Patients with PD-L1 expression ≧ 1% have a loner mPFS than those with PD-L1 expression <1% or unknown (10.6 months vs. 2.5 months vs. 7.8 months; p < 0.001). There were no significant differences in response rates and PFS between patients with and without malignant pleural effusion, liver, or brain metastasis.
Conclusions
The combination treatment of atezolizumab, bevacizumab, pemetrexed, and cisplatin/carboplatin provided favorable efficacy in EGFR mutation-positive NSCLC after TKI failure, and higher PD-L1 expression (≧ 1%) was associated with longer PFS.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, Novartis, Eli Lilly, Roche. C. Ho: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, AstraZeneca, Eli Lilly, Amgen, Roche/Genentech, Merck Sharp & Dohme, Pfizer, Novartis, Bristol-Myers Squibb, Ono Pharmaceuticals. W. Liao: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Pfizer, Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Chugai Pharma Taiwan. J.C. Yang: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, AstraZeneca, Roche/Genentech, Pfizer, Novartis, Merck Sharp & Dohme, Merck Serono, Clovis Oncology, Bayer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, AstraZeneca, Roche/Genentech, Pfizer, Novartis, Merck Sharp & Dohme, Merck Serono, Clovis Oncology, Bayer. J. Shih: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Ono Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Ono Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb. All other authors have declared no conflicts of interest.
30P - Real-world disease characteristics and treatment patterns in patients with advanced non-small cell lung cancer and EGFR in Brazil and Taiwan
- H. BAILEY (Bollington, United Kingdom)
- H. BAILEY (Bollington, United Kingdom)
- H. Burlison (BOLLINGTON, United Kingdom)
- S. Chandrasekar (Cambridge, United States of America)
- C. Wong (Singapore, Singapore)
- C. Forshaw (BOLLINGTON, United Kingdom)
- K. Duncan (Cambridge, United States of America)
Abstract
Background
Advanced non-small cell lung cancer (aNSCLC) treatment (tx) decision-making is complex, with prognosis and tx influenced by molecular alterations. Data are limited on how epidermal growth factor receptor mutation (EGFRm) subtypes influence tx choice in clinical practice. We aimed to describe disease characteristics and tx patterns in aNSCLC patients (pts) with EGFRm.
Methods
Data were drawn from the Adelphi NSCLC Disease Specific Programme™, a point-in-time survey of oncologists/pulmonologists, collected in Brazil and Taiwan from Jul-Nov 2020. Physicians reported characteristic and tx data for the next 5 consulting adult aNSCLC pts with EGFRm, including pts with point-mutation in exon 21 (exon 21) and/or deletion in exon 19 (exon 19). Data analysis was descriptive.
Results
Of 471 pts, 26% (n = 124) had exon 21 and 35% (n = 167) had exon 19. Median age was 65.0 years, 57% were female and 87% had adenocarcinoma. At aNSCLC diagnosis, 77% were stage IV and 69% had an Eastern Cooperative Oncology Group performance status of 0–1. EGFR tyrosine kinase inhibitor (TKI) monotherapy (mono) was the most common first-line (1L) tx; 41% of pts received first generation (1G), 21% second generation (2G) and 16% third generation (3G) EGFR TKI regardless of mutation type. 26% of exon 21 and 27% of exon 19 pts received 2G EGFR TKI, while 9% and 21%, respectively, received 3G EGFR TKI. Of pts who completed 1L tx (n = 55), most (84%) had partial response regardless of mutation type (94% of exon 21, n = 15; 84% of exon 19, n = 21). Median time to discontinuation (TTD) of 1L was 14.2 months (mo) overall (n = 61); 17.1 mo in exon 21 (n = 16) and 16.0 mo in exon 19 (n = 27). Median time to next tx was 15.0 mo overall (n = 61); 19.0 mo in exon 21 (n = 15) and 17.0 mo in exon 19 (n = 27). Median real-world progression free survival (excluding death; rwPFS) was 15.1 mo overall (n = 61); 19.2 mo in exon 21 (n = 15) and 16.6 mo in exon 19 (n = 27).
Conclusions
Pts with EGFRm generally received EGFR TKI mono, including those with exon 21 and exon 19. Exon 21 pts had longer TTD and rwPFS (no formal comparison was made between groups). Future research should examine whether different sensitizing EGFR mutations have an impact on pt outcomes.
Legal entity responsible for the study
Adelphi Real World.
Funding
Adelphi Real World.
Disclosure
H. Bailey: Financial Interests, Institutional, Full or part-time Employment: Adelphi. H. Burlison: Financial Interests, Institutional, Full or part-time Employment: Adelphi. S. Chandrasekar: Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Institutional, Full or part-time Employment: Pfizer. C.H. Wong: Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Institutional, Full or part-time Employment: Pfizer. C. Forshaw: Financial Interests, Institutional, Full or part-time Employment: Adelphi. K. Duncan: Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Institutional, Full or part-time Employment: Pfizer.
31P - EGFR mutation rate and spectrum in Ukrainian patients with advanced NSCLC: Relation to gender and PD-L1 expression
- S. Livshun (Kyiv, Ukraine)
- S. Livshun (Kyiv, Ukraine)
- A. Matvieieva (Kyiv, Ukraine)
- D. Kaminskyi (Kyiv, Ukraine)
- D. Kozakov (Kyiv, Ukraine)
- R. Shabalkov (Kyiv, Ukraine)
- O. Koshyk (Kyiv, Ukraine)
- O. Sulaieva (Kyiv, Ukraine)
Abstract
Background
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and immunotherapy are the core options for advanced non-small cell lung cancer (NSCLC) treatment. The efficacy of EGFR-TKI therapy was shown to vary depending on sex. And furthermore, EGFR alterations can impact PD-L1 expression and immunotherapy benefits. The aim of this study was to investigate the prevalence of clinically actionable EGFR mutations and their relation to PD-L1 expression with respect to gender in the Ukrainian cohort.
Methods
This retrospective study included 907 patients, diagnosed with advanced NSCLC who were tested for EGFR mutations and PD-L1 expression. There were 797 patients (87,9%) with adenocarcinoma (AC), 101 patients (11,1%) with squamous cell carcinoma (SCC) and 9 individuals (1%) with large cell neuroendocrine carcinoma (LC-NEC). EGFR mutation status in tissue samples was assessed by either NGS (n = 83) or qPCR (n = 824). PD-L1 testing was performed by IHC.
Results
SCC rate was higher in males (13,3% vs 8,4%), females demonstrated prevalence of AC (91,1% vs 85,3%; P = 0,022). 78 (21,5%) out of 363 women with AC were under 50 y.o., while only 65 out of 434 (15%) men were younger than 50 at the time of AC diagnosis (P = 0,027). 198 out of 907 patients (21,8%) had EGFR-mutant NSCLC. Patients with AC harbored EGFR mutations twice as frequently (187 out of 797 patients; 23,5%) as compared to SCC (9 out of 101; 8,9%; P = 0,004). There was no statistically significant difference in PD-L1 expression between NSCLC of different histology and EGFR status. EGFR mutation rate was higher in females (35,5%) compared to males (11,2%; P < 0,001). The Ex19del and L858R variants predominated in both males and females. However, females demonstrated a higher rate of sensitizing EGFR mutations (87,9% vs 71,9% in males). Males with NSCLC carried more exon 20 alterations, including in-frame insertions and T790M mutation (15,8% vs 4,3% in females) and presented uncommon variants including G719X, L861Q and S768I (10,5% vs 4,3%) more frequently (P = 0,009).
Conclusions
There are profound gender differences in the rates and spectrum of EGFR mutations in NSCLC with no relation to PD-L1 expression. Gender differences in EGFR mutation landscape can affect response to treatment.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
32P - Atezolizumab plus albumin paclitaxel-based regimens is an optional treatment for EGFR-mutant patients with SCLC transformation after EGFR-TKI
- J. Wang (Beijing, China)
- J. Wang (Beijing, China)
- Y. Wang (Beijing, China)
Abstract
Background
SCLC transformation is one of the acquired resistance mechanisms for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients. It remains unclear whether the addition of atezolizumab to chemotherapy could prolong PFS and OS of patients with SCLC transformation after EGFR-TKI treatment.
Methods
Three groups of advanced lung adenocarcinoma patients who relapsed after EGFR-TKI were analyzed in this retrospective study: cohort A included patients who did not undergo SCLC transformation and received atezolizumab plus chemotherapy after EGFR-TKI; cohort B included patients with SCLC transformation and following atezolizumab treatment; cohort C included patients who underwent SCLC transformation and did not receive atezolizumab treatment.
Results
Twenty-six patients were enrolled in this research (cohort A: N = 6; cohort B: N = 6; cohort C: N = 14). Five of six patients in group A and all patients of group B received atezolizumab plus albumin paclitaxel-based regimens. In addition, five of six patients received atezolizumab plus albumin paclitaxel-based regimens after conventional etoposide/platinum treatment. Etoposide/platinum +/− EGFR-TKI regimens were given to all patients in group C as first-line treatment after SCLC transformation. DCR (83.3% vs 100.0%, p = 0.224) and ORR (0% vs 16.7%, p = 0.224) were similar between cohort A and cohort B. Comparable median PFS (3.5 m vs 4.7 m, p = 0.086), median OS from diagnosis of advanced stage lung cancer (33.7 m vs 54.3 m, p = 0.077), and median OS from atezolizumab implementation (6.7 vs 7.6 m, p = 0.627) were observed between group A and group B. No significant differences in median PFS between group B and group C (4.7 m vs 3.5 m, p = 0.754). Patients in cohort B presented a tendency to have better median OS from diagnosis of stage IV lung cancer (45.4 m vs 22.5 m, p = 0.180) and better median OS from SCLC transformation (24.1 m vs 11.5 m, p = 0.092) compared with cohort C.
Conclusions
In patients with SCLC transformation after EGFR-TKI, atezolizumab plus albumin paclitaxel-based regimen was a treatment choice after conventional etoposide/platinum regimens.
Legal entity responsible for the study
Y. Wang.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
33P - Real-world experience of MET TKI-induced peripheral edema
- R. Ferrara (Milan, Italy)
- R. Ferrara (Milan, Italy)
- J. F. Vansteenkiste (Leuven, Belgium)
- X. Yang (Beijing, China)
- F. Grossi (Varese, Italy)
- B. Melosky (Vancouver, Canada)
- M. Ahn (Seoul, Korea, Republic of)
- A. Calles (Madrid, Spain)
- O. S. Chan (Hong Kong, Hong Kong PRC)
- B. Han (Shanghai, China)
- V. Bulusu (Cambridge, United Kingdom)
- R. Califano (Manchester, United Kingdom)
- K. Nishino (Osaka, Japan)
- V. Ghori (Darmstadt, Germany)
- P. Ronga (Darmstadt, Germany)
- K. Berghoff (Darmstadt, Germany)
- S. Vlassak (Darmstadt, Germany)
- X. Le (Houston, United States of America)
Abstract
Background
Peripheral edema (PE), a class effect of MET TKIs, can impact treatment (tx) adherence. We conducted the Powerhouse Insights from Virtual Oncology Therapeutic Specialists (PIVOTS) survey of physicians’ experience with MET TKIs to better understand associated PE and optimize its management.
Methods
An online survey assessed onset, time to resolution, symptoms, prevention, and management of PE during tx with four available MET TKIs for MET exon 14 skipping NSCLC (tepotinib, capmatinib, savolitinib and crizotinib).
Results
In total, 26 physicians participated: Asia (14), Europe (6), UK (2) and North America (4). 24 physicians had experience with tepotinib, 10 with savolitinib, 20 each with capmatinib and crizotinib, and 7 with all four MET TKIs. Six physicians had experience with >20 patients (pts), 9 with 10–20 pts, 6 with 5–10 pts and 5 with <5 pts treated with a MET-TKI. 77% of physicians reported that >50% of pts had PE with MET TKIs. Low mobility, age, and time on tx were reported as common risk factors, and cardiac disease as the most common comorbidity. PE onset, which may take >6 months, and time to improvement was considered similar among MET-specific TKIs, with crizotinib (a multi-kinase TKI) resulting in less frequent, less severe, and less durable PE. Swollen extremities were reported by 96% of physicians as the most bothersome symptom followed by pain (46%) and weight gain (31%), with a resolution time of up to 3 months in mild-moderate PE and up to 6 months in severe PE. Pain (81% vs 23%) and skin lesions (50% vs 23%) were reported as more common in severe vs mild-moderate PE, respectively. 62% of physicians incorporated multiple preventive measures simultaneously (bed/feet elevation [88%], compression stockings [69%], massage [63%], salt intake reduction [50%], exercise/diuretics [25%]); only 13% incorporated at tx initiation. The most common tx were diuretics (89%), non-pharmacologic measures (85%), MET TKI interruption (73%) and dose reduction (65%); 4/5 Chinese physicians reported consulting vascular specialists.
Conclusions
The PIVOTS survey indicates the most important unmet needs for PE management are developing effective tx, incorporating preventive measures at MET TKI initiation (not only at PE onset), and clarity of its mechanism of action associated with MET TKI.
Editorial acknowledgement
Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Pritha Bhunia of Syneos Health, London, UK.
Legal entity responsible for the study
Merck Healthcare KGaA, Darmstadt, Germany.
Funding
Merck Healthcare KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).
Disclosure
R. Ferrara: Non-Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, BeiGene. J.F. Vansteenkiste: Non-Financial Interests, Personal, Advisory Board: Merck Healthcare KGaA, Darmstadt, Germany. X. Yang: Non-Financial Interests, Personal, Other, Honoraria for lectures/advisory boards/consultancy: Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, AstraZeneca, BeiGene, HengRui, XinDa. F. Grossi: Non-Financial Interests, Personal, Other, Advisory Role/Ad Hoc Advisory Boards/Consultations (last 3 years): Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, Pierre Fabre, Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Otsuka, Takeda, Bayer; Non-Financial Interests, Personal, Other, Honoraria: Seminar/Talks to Industry (last 3 years): Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, Pierre Fabre, Amgen, Celgene, Bristol-Myers Squibb, Merck Sharpe & Dohme; Financial Interests, Personal, Research Grant: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme. B. Melosky: Non-Financial Interests, Personal, Advisory Role: AstraZeneca, Takeda, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, EMD Serono, an affiliate of Merck KGaA, Pfizer. M. Ahn: Non-Financial Interests, Personal, Other, Consulting and advisory role: AstraZeneca, Eli Lilly, Amgen, Merck Healthcare KGaA, Darmstadt, Germany, Merck Sharpe & Dohme, Takeda, Ono, Pfizer, Yuhan, Alpha-pharmaceuticals, Daiichi Sankyo, Roche. A. Calles: Non-Financial Interests, Personal, Other, Consulting or advisory role: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Eli Lilly, Takeda, Novartis, Merck Sharp & Dohme, Bristol-Myers Squibb. O.S.H. Chan: Non-Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme, AstraZeneca, Novartis, Amgen, Merck Healthcare KGaA, Darmstadt, Germany; Non-Financial Interests, Personal, Advisory Board: Pfizer, Merck Healthcare KGaA, Darmstadt, Germany, Takeda, Janssen. R. Califano: Non-Financial Interests, Personal, Other, Consulting or advisory role: AstraZeneca, Sanofi, Pfizer, Roche, Eli Lilly, Takeda, Novartis, Merck Sharp & Dohme, Bristol-Myers Squibb, Janssen, PharmaMar, Amgen. K. Nishino: Non-Financial Interests, Personal, Other, Honoraria for lectures: Merck Healthcare KGaA, Darmstadt, Germany, AstraZeneca, Chugai pharmaceutical, Nippon Boehringer Ingelheim, Eli Lilly Japan, Roche Diagnostics, Novartis, Pfizer, Janssen Pharmaceutical K.K., Bristol Myers Squibb, Nippon Kayaku; Financial Interests, Personal, Research Grant: Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Merck Sharp & Dohme, AbbVie, Daiichi Sankyo Company, Limited, Amgen, Eisai Co., Ltd., Sanofi K.K., Janssen Pharmaceutical K.K., Novartis, Pfizer, Merck Healthcare KGaA, Darmstadt, Germany, Takeda, Eli Lilly Japan, Chugai pharmaceutical, Merus. V. Ghori: Non-Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. P. Ronga: Non-Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. K. Berghoff: Non-Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. S. Vlassak: Non-Financial Interests, Personal, Full or part-time Employment: Merck N.V.-S.A., Belgium, an affiliate of Merck Healthcare KGaA, Darmstadt, Germany. X. Le: Non-Financial Interests, Personal, Other, Consulting/advisory role: Sanofi Aventis, Merck Sharp and Dohme, Takeda, Amgen, Boehringer Ingelheim. All other authors have declared no conflicts of interest.
34P - Treatment sequencing in the VISION study of tepotinib in patients with MET exon 14 (METex14) skipping NSCLC
- F. Griesinger (Oldenburg, Germany)
- F. Griesinger (Oldenburg, Germany)
- M. C. Garassino (Chicago, United States of America)
- E. Felip (Barcelona, Spain)
- H. Sakai (Kitaadachi-gun, Japan)
- X. Le (Houston, United States of America)
- R. Veillon (Pessac, France)
- E. F. Smit (Leiden, Netherlands)
- J. Raskin (Edegem, Belgium)
- M. Thomas (Heidelberg, Germany)
- M. Ahn (Seoul, Korea, Republic of)
- S. Vlassak (Darmstadt, Germany)
- R. Bruns (Darmstadt, Germany)
- A. Johne (Darmstadt, Germany)
- P. K. Paik (New York, United States of America)
Abstract
Background
Tepotinib is a MET TKI approved for METex14 skipping NSCLC. We report Tx sequencing prior/post tepotinib of immunotherapy (IO), chemotherapy (CT) and METi (post only) in VISION (data cut-off: Feb 20, 2022).
Methods
Pts with advanced/metastatic METex14 skipping NSCLC received 500 mg (450 mg active moiety) tepotinib QD. Primary endpoint: objective response (RECIST 1.1) by IRC. Prior/post tepotinib Tx was investigator's choice; outcomes were reported per investigator.
Results
Of 313 pts (median age 72), 164 were Tx naïve (median age 74) and 149 previously treated (median age 70.8). Among previously treated pts, the most common 1L regimen prior to enrolling in VISION was platinum-CT without IO (58%), then IO monotherapy (23%) and IO-CT (13%). Across all prior 1L regimens, median duration of Tx was 4 mo (IQR 1.8–7.3), with an ORR of 24.8%, mDOR of 6.0 mo (IQR 4–12) and mPFS of 4.0 mo (IQR 2–8.5) (outcomes by Tx regimen in table). In contrast, 1L outcomes to tepotinib were greatly improved with an ORR of 56.1%, mDOR of 46.4 mo and mPFS of 12.6 mo. Overall, 265 pts (84.7%) discontinued tepotinib; 124 pts (46.8%) received subsequent Tx. 48 pts received subsequent METi (20 crizotinib, 15 capmatinib, 4 bozitinib, 3 tepotinib, 3 amivantamab, 3 cabozantinib, 4 other; 4 pts received different METi in subsequent lines). 31 pts received subsequent METi immediately after tepotinib (11 1L and 20 2L+ pts). BOR across all subsequent METi was 3 PR (1 pt received METi immediately after tepotinib, 2 pts received CT/IO regimens followed by METi), 11 SD; longest mDOR and mPFS were 4.0 and 2.5 mo, respectively. Outcomes to subsequent CT/IO were comparable to outcomes of prior CT/IO as well as those reported in literature.
| Outcomes with: | No. pts receiving Tx | ORR, % | mDOR, mo | mPFS, mo |
|---|---|---|---|---|
| 1L Tx | ||||
| IO+platinum CT | 19 | 26.3 | 5.0 | 5.0 |
| IO mono | 34 | 23.5 | 7.5 | 5.0 |
| Platinum-CT without IO | 87 | 27.6 | 5.0 | 4.0 |
| Tepotinib by IRC | ||||
| 1L | 164 | 56.1 | 46.4 | 12.6 |
| 2L | 92 | 45.7 | 12.6 | 10.9 |
| +3L | 57 | 43.9 | 10.8 | 11.0 |
| Post tepotinib Tx by investigator assessment | ||||
| Subsequent CT | 31 | 6.5 | 3.0 | 2.0 |
| Subsequent IO | 43 | 14.0 | 8.0 | 3.0 |
9 patients received other 1L Tx. CT, chemotherapy; IO, immunotherapy; Tx, treatment.
Conclusions
Robust and durable efficacy, particularly in the 1L setting, support early use of tepotinib in Tx sequence. Almost half of this elderly population received subsequent Tx, higher than the 20–30% reported for 1L CT/IO IPSOS trial in elderly pts (median age 75). METi Tx sequencing analyses ongoing.
Clinical trial identification
NCT02864992.
Editorial acknowledgement
Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Syneos Health, London, UK.
Legal entity responsible for the study
Merck Healthcare KGaA, Darmstadt, Germany.
Funding
Merck Healthcare KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).
Disclosure
F. Griesinger: Non-Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, GSK, Eli Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda; Non-Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Celgene, GSK, Eli Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda; Financial Interests, Personal, Research Grant: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, GSK, Eli Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda. M.C. Garassino: Non-Financial Interests, Personal, Other, Honoraria: MSD Oncology, AstraZeneca/MedImmune, GlaxoSmithKline, Takeda, Roche, Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, MSD, AstraZeneca, Novartis, Takeda, Roche, Tiziana Life Sciences, Sanofi-Aventis, Celgene, Daiichi Sankyo, Inivata, Incyte, Pfizer, Seattle Genetics, Eli Lilly, GlaxoSmithKline, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, Janssen, Regeneron; Non-Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Takeda, MSD Oncology, Celgene, Incyte, Roche, Bristol Myers Squibb, Otsuka, Eli Lilly; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, MSD, Roche/Genentech, AstraZeneca/MedImmune, AstraZeneca, Pfizer, GlaxoSmithKline, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Incyte, Takeda, Spectrum Pharmaceuticals, Blueprint Medicine, Eli Lilly, Ipsen, Janssen, Exelixis, MedImmune, Sanofi, Pfizer, Amgen; Financial Interests, Personal, Other, Travel, accommodation, expenses: Pfizer, Roche, AstraZeneca. E. Felip: Non-Financial Interests, Personal, Advisory Role: Pfizer, Roche, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Guardant Health, Novartis, Takeda, AbbVie, Blueprint Medicines, Eli Lilly, Merck Healthcare KGaA, Darmstadt, Germany, Merck Sharp & Dohme, Janssen, Samsung; Non-Financial Interests, Personal, Speaker's Bureau, and expert testimony: Pfizer, Roche, AstraZeneca, Bristol Myers Squibb, Novartis, Takeda, Eli Lilly, Merck Sharp & Dohme, Medscape, prIME Oncology, Touchtime; Financial Interests, Personal, Research Grant: Fundación Merck Salud, a private non-profit institution founded by Merck, S.L.U., Madrid, Spain, an affiliate of Merck KGaA, Grant for Oncology Innovation (GOI); Non-Financial Interests, Personal, Officer, Officer/Board of Directors: Grifols (Independent Member). H. Sakai: Non-Financial Interests, Personal, Speaker's Bureau: Bristol Myers Squibb, Ono Pharmaceutical, MSD K.K., AstraZeneca, Chugai Pharma, Taiho Pharmaceutical, Boehringer Ingelheim. X. Le: Non-Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, EMD Serono, an affiliate of Merck KGaA, Novartis, Daiichi Sankyo, Hengrui Therapeutics; Financial Interests, Personal, Research Grant: Eli Lilly, Boehringer Ingelheim. R. Veillon: Non-Financial Interests, Personal, Advisory Role: MSD, Pfizer, Novartis; Non-Financial Interests, Personal, Speaker's Bureau: MSD, Bristol Myers Squibb, Roche; Financial Interests, Personal, Research Grant: Roche, Takeda, AbbVie, Merck Healthcare KGaA, Darmstadt, Germany, Bristol Myers Squibb. E.F. Smit: Non-Financial Interests, Institutional, Advisory Role: Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol Myers Squibb, Merck Healthcare KGaA, Darmstadt, Germany, MSD Oncology, Takeda, Bayer, Regeneron, Novartis, Daiichi Sankyo, Seattle Genetics; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Roche/Genentech, AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Bayer. J. Raskin: Non-Financial Interests, Personal, Advisory Role: Pfizer, Eli Lilly; Non-Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Bristol Myers Squibb; Financial Interests, Personal, Other, Travel expenses: Roche. M. Thomas: Non-Financial Interests, Personal, Other, Honoraria – Scientific Meetings: AbbVie, Bristol Myers Squibb, MSD, AstraZeneca, Novartis, Roche, Takeda, Eli Lilly, Chugai, Celgene, Boehringer Ingelheim, Pfizer, Janssen, GSK, Merck Healthcare KGaA, Darmstadt, Germany, Sanofi, Amgen; Financial Interests, Personal, Other, Travelling support: AbbVie, Bristol Myers Squibb, MSD, AstraZeneca, Novartis, Roche, Takeda, Eli Lilly, Chugai Pharma, Celgene, Boehringer Ingelheim, Pfizer; Non-Financial Interests, Personal, Advisory Board: AbbVie, Bristol Myers Squibb, MSD, AstraZeneca, Novartis, Roche, Takeda, Eli Lilly, Chugai Pharma, Celgene, Boehringer Ingelheim, Pfizer, Janssen, Daiichi Sankyo, GSK, Merck Healthcare KGaA, Darmstadt, Germany, Sanofi, Amgen; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca, Roche, Takeda. M. Ahn: Non-Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, Amgen, Merck KGaA Darmstadt, Germany, MSD, Takeda, ONO, Pfizer, YUHAN, Alpha-pharmaceuticals, Daiichi Sankyo, Roche. S. Vlassak: Financial Interests, Personal, Full or part-time Employment: Merck N.V.-S.A., Belgium, an affiliate of Merck KGaA Darmstadt, Germany. R. Bruns: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Stocks/Shares: Merck Healthcare KGaA, Darmstadt, Germany. A. Johne: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Stocks/Shares: Novartis. P.K. Paik: Non-Financial Interests, Personal, Advisory Role: Takeda, Xencor, CrownBio, Bicara, Mirati, EMD Serono, an affiliate of Merck KGaA; Financial Interests, Institutional, Research Grant: Bicara, Boehringer Ingelheim, EMD Serono, an affiliate of Merck KGaA.
35P - Drug treatment management of advanced ALK-positive non-small cell lung cancer in Spain: A real-world cross-sectional analysis
- M. E. Olmedo Garcia (Madrid, Spain)
- M. E. Olmedo Garcia (Madrid, Spain)
- U. Asensio (Madrid, Spain)
- L. García (Madrid, Spain)
- P. Rebollo (Madrid, Spain)
- I. Ricote (Madrid, Spain)
- G. Cárdenas (Barcelona, Spain)
- C. Marcos (Madrid, Spain)
Abstract
Background
In Spain, new generation ALK inhibitors have been added as new therapeutic options, with specific indications, to those already available for advanced or metastatic ALK-positive non-small cell lung cancer (mNSCLC ALK+). In this context it is key to understand current treatment management of this subpopulation by line in clinical practice, as well as the most prescribed treatment sequences, as in most cases they have not been fully established.
Methods
This is a cross-sectional, population-based observational study, based on IQVIA Oncology Advantage dataset, that includes drug-treated anonymized mNSCLC ALK+ patient cases in real clinical practice reported by senior physicians at a quarterly basis in Spain. The sample of 368 mNSCLC ALK+ patients reported between July 2021 and June 2022 was selected for the study. Patients participating in phase II or III clinical trials were excluded (N = 29). A descriptive analysis of all therapeutic regimens prescribed by line was performed (1L, 2L, and 3L+, respectively), using absolute and relative frequencies, as well as an identification of main treatment sequences across lines based on the subpopulation currently on 2L+.
Results
A sample of 339 patients was analyzed, 163 in 1L, 90 in 2L and 86 in 3L+. Patients were mostly treated in 1L with alectinib (N/%) (138/85%), followed by brigatinib (8/5%), the share of the first ALK inhibitor commercialized, crizotinib, of being 4% nowadays. In 2L, alectinib (29/32%), lorlatinib (27/30%), and brigatinib (9/10%) were the most prescribed treatments; and in 3L+, immunotherapy (IO) (27/31%), lorlatinib (18/21%), and platinum-based regimens (18/21%). The most common sequence from 1L to 2L among patients currently on 2L was alectinib-lorlatinib (27/30%). Among patients currently on 3L+, the most prescribed sequences 1L-2L-3L+ were crizotinib-alectinib-lorlatinib (12/14%), and crizotinib-alectinib-IO or alectinib-lorlatinib-IO both in the same proportion (8/9%).
Conclusions
New drugs marketed in Spain for mNSCLC ALK+ patients seem to have gained importance in 2L and 3L. Additional approvals are expected so clinical practice could continue evolving.
Legal entity responsible for the study
IQVIA Information S.A
Funding
Pfizer S.L.U
Disclosure
M.E. Olmedo: Non-Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol-Myers Squibb, MSD, Sanofi; Non-Financial Interests, Personal, Speaker's Bureau: Roche, AstraZeneca, Bristol-Myers Squibb, MSD, Pfizer. Ú. Asensio: Non-Financial Interests, Personal, Full or part-time Employment: Pfizer. L.F. García: Non-Financial Interests, Personal, Full or part-time Employment: Pfizer. All other authors have declared no conflicts of interest.
36P - Prevalence, clinical characteristics, and treatment outcomes of patients with BRAF-mutated advanced NSCLC in China: A real-world multi-center study
- B. Jia (Beijing, China)
- B. Jia (Beijing, China)
- J. Zhao (Beijing, China)
- B. Jin (Shenyang, China)
- F. Zhang (Shenyang, China)
- S. Wang (Shenyang, China)
- L. Zhang (Shenyang, China)
- Z. Wang (Beijing, China)
- T. An (Beijing, China)
- Y. Wang (Beijing, China)
- M. Zhuo (Beijing, China)
- J. Li (Beijing, China)
- X. Yang (Beijing, China)
- S. Li (Beijing, China)
- H. Chen (Beijing, China)
- Y. Chi (Beijing, China)
- J. Wang (Beijing, China)
- X. Zhai (Beijing, China)
- Y. Tai (Beijing, China)
- Y. Liu (Beijing, China)
- G. Guan (Beijing, China)
Abstract
Background
BRAF mutation is one of the targetable oncogenic driver mutations in non-small-cell lung cancer (NSCLC). However, the prevalence, real-world treatments and clinical outcomes are rarely reported in Chinese BRAF-mutated NSCLC patients.
Methods
The next-generation sequencing (NGS) data of 137,798 Chinese NSCLC patients from the Lung Cancer Big Data Precise Treatment Collaboration Group (LANDSCAPE) project (Cohort I) were analyzed to derive the prevalence of BRAF mutations. We also retrospectively collected clinical and survival data of 129 advanced NSCLC patients with primary BRAF mutation from two centers between December 2015 and September 2022 (Cohort II). Baseline characteristics, treatment pattern and outcomes were analyzed in Cohort II.
Results
In Cohort I, 4409 patients (3.2%) were confirmed to harbor a BRAF mutation. BRAF V600E accounted for 28.7% of all BRAF mutation. In Cohort II, 62% (80/129) were BRAF V600 mutation with median age of 63.0 years. Of 99 patients who receive NGS, 79 (79.8%) patients had concomitant mutations, with TP53 of the highest incidence (33.3%). For patients received first-line dabrafenib plus trametinib (dab-tram) (N = 38), the median progression-free survival (PFS) was 25.0 months (95%CI: 13-NA), which is significantly longer than chemotherapy (N = 38, mPFS 8.4 months, 95%CI: 6.3–19.2, P = 0.023) and other regimens (N = 11, mPFS 8.0 months, 95%CI: 7.8-NA, P = 0.046). A numerically longer mPFS was also observed with dab-tram versus immunotherapy based therapy (N = 22, mPFS 11.4 months, 95%CI: 7.8-NA, P = 0.25). After applying inverse probability of treatment weighting (IPTW), the above differences still existed.
Conclusions
In the study with the largest sample size so for, 3.2% of Chinese NSCLC patients were observed to have BRAF mutations. The more favorable PFS benefit demonstrated by first-line dabrafenib plus trametinib compared with all other therapy regimens indicates the optimal treatment choice for Chinese BRAF-mutated NSCLC patients.
Legal entity responsible for the study
Peking University Cancer Hospital.
Funding
Science Foundation of Peking University Cancer Hospital.
Disclosure
All authors have declared no conflicts of interest.
37P - Pralsetinib in acquired RET fusion-positive advanced non-small cell lung cancer patients after resistance to EGFR/ALK-TKI: A China multi-center, real-world data (RWD) analysis
- J. Hu (Shanghai, China)
- J. Hu (Shanghai, China)
- X. TANG (Shanghai, China)
- R. Guo (Nanjing, China)
- Y. Wang (Hangzhou, China)
- H. Shen (Ningbo, China)
- H. Wang (Tianjin, China)
- Y. Yao (Xi'an, China)
- X. Cai (Dalian, China)
- Z. Yu (Qingdao, China)
- G. Dong (Tangshan, China)
- F. Liang (Shanghai, China)
- J. Cao (Yiyang, China)
- L. Zeng (Changsha, China)
- M. Su (Shenzhen, China)
- W. Kong (Fuzhou, China)
- L. Liu (Nanning, China)
- W. Huang (Ningbo, China)
- C. Cai (Wenzhou, China)
- Y. Xie (Wenzhou, China)
- W. Mao (Wuxi, China)
Abstract
Background
RET-fusion was reported contribute about 2% of acquired resistance mechanisms of EGFR/ALK-TKIs. Selective RET inhibitor pralsetinib demonstrated impressive improvement of survival in patients with RET+ aNSCLC in the I/II ARROW study. However, the efficacy in patients with acquired RET-fusion after resistance to EGFR/ALK-TKIs was only reported by case, and the strategy of overcome the acquired RET-fusion has not been fully investigated.
Methods
This multicenter, retrospective, real-world data analysis enrolled thirty-one aNSCLC with acquired RET-fusion after resistance to EGFR/ALK-TKIs in 23 centers across China from Jan 1st, 2015 to Nov 23rd, 2022. Cohort 1 including 20 patients who received pralsetinib immediately after RET-fusion was detected, of which 15 patients received pralsetinib combined with EGFR/ALK-TKI. Eleven patients who underwent standard chemotherapy in combination with or without immunotherapy or antiangiogenesis therapy on acquired RET+ occurred were enrolled in Cohort 2. Molecular profile, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), time to treatment failure (TTF), toxicity was assessed.
Results
25.8% (8/31) patients lost EGFR mutation when RET-fusion was detected. EGFR 19del (64.5%) was more likely to develop acquired RET+ compared with L858R mutation (29.0%). CCDC6 was the most common RET-partners (38.7%), followed by KIF5B (19.4%), and NCOA4 (16.1%). In Cohort 1, ORR was 35.0% and DCR was 75.0%, which were higher than Cohort 2 (18.2% and 54.6%, respectively). Patients who received pralsetinib-based therapy had a longer PFS and TTF compared with patients in cohort 2 (PFS: 8.42 months vs. 6.97 months, TTF: 6.48 months vs. 4.24 months). Pralsetinib and EGFR-TKI combination therapy was generally well tolerated, with AEs consistent with known profile of the two drugs.
Conclusions
Pralsetinib-based therapy may be a potential strategy to overcome the acquired RET-fusion after resistance of EGFR/ALK-TKIs.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
38P - Matching-adjusted indirect comparison (MAIC) of treatment outcomes for selective RET inhibitors, selpercatinib and pralsetinib, in non-small cell lung cancer (NSCLC)
- M. J. Hochmair (Vienna, Austria)
- M. J. Hochmair (Vienna, Austria)
- E. Nadal (L'Hospitalet de Llobregat, Spain)
- Y. D'yachkova (Indianapolis, United States of America)
- T. Puri (Indianapolis, United States of America)
- A. Vickers (Manchester, United Kingdom)
- S. Wolowacz (Manchester, United Kingdom)
- X. Wang (Indianapolis, United States of America)
- U. Kiiskinen (Indianapolis, United States of America)
Abstract
Background
Selpercatinib (SELP) and pralsetinib (PRAL) are approved for RET fusion-positive advanced NSCLC, based on the LIBRETTO-001 and ARROW trials. No randomized direct comparison of SELP and PRAL is available or ongoing.
Methods
MAIC was conducted between the NSCLC data from LIBRETTO-001 (June 2021 datacut) and ARROW (March 2022 datacut). LIBRETTO-001 results were weighted to match ARROW baseline characteristics. Objective response rate (ORR), progression-free and overall survival (PFS and OS) were compared for treatment-naive (TN) and platinum-pretreated (PP) cohorts using 95% confidence intervals for hazard ratios (HR) and odds ratios (OR). Safety was also compared.
Results
Weighted ORRs were similar for SELP and PRAL, as were PFS and OS in TN patients (table). In PP patients, PFS and OS were significantly longer for SELP. There were fewer grade ≥3 treatment-related adverse events (TRAE) and lower rates of treatment discontinuation due to TRAE in patients receiving SELP. The difference in % of Asian patients impacted weighted results.
Comparative efficacy and safety for SELP and PRAL in RET fusion-positive NSCLC estimated by MAIC
| Study measure, (95% CI) | SELP | PRAL | OR/HR Comparison (SELP vs PRAL) | |||
|---|---|---|---|---|---|---|
| TN (Neff = 37) | PP (Neff = 193) | TN (n = 116) | PP (n = 141) | TN | PP | |
| ORR, % | 77.1 | 59.2 | 72.4 | 59.6 | 1.29 | 0.98 |
| (67.4, 90.1) | (53.5, 64.7) | (63.3, 80.3) | (51.0, 67.7) | (0.67,4.06) | (0.70,1.43) | |
| Median PFS, mo | 17.1 | 24.9 | 12.5 | 16.3 | 0.81 | 0.67 |
| (11.5, 22.0) | (19.3, NR) | (9.2, 16.5) | (10.8, 22.2) | (0.52, 1.26) | (0.50, 0.90)* | |
| Median OS, mo | 32.3 | NR | NR | 44.3 | 1.20 | 0.68 |
| (18.5, NR) | (30.3, NR) | (31.9, NR) | (25.0, NR) | (0.69, 2.09) | (0.48, 0.97)* | |
| SELP NSCLC Safety Population | PRAL NSCLC Safety Population | OR (95% CI) | ||||
| (Neff = 247) | (N = 281) | |||||
| Grade ≥3 TRAEs, % | 39.3 | 62.6 | 0.39 | |||
| (34.8, 43.9) | (56.7, 68.3) | (0.29,0.49)* | ||||
| Discontinuation due to TRAEs, % | 3.6 | 10.0 | 0.34 | |||
| (1.4, 5.4) | (6.7, 14.1) | (0.14,0.58)* |
Conclusions
The efficacy of SELP and PRAL was similar. SELP was associated with fewer grade ≥3 TRAE and treatment discontinuations due to TRAE. Inherent limitations of MAIC are acknowledged.
Clinical trial identification
LIBRETTO 001 NCT03157128 ARROW NCT03037385.
Editorial acknowledgement
Medical writing and editing assistance was provided by Sara Musetti Jenkins and Paul Hobson, respectively, of RTI Health Solutions.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
M.J. Hochmair: Financial Interests, Personal, Invited Speaker: Eli Lilly and Company, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Roche, and Takeda; Financial Interests, Personal, Advisory Board: Eli Lilly and Company, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Roche, and Takeda. E. Nadal: Financial Interests, Personal, Research Grant: Roche, Pfizer, Merck Serono, BMS; Financial Interests, Personal, Other, Consulting fees: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Sanofi, Pfizer, Eli Lilly, Amgen, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Janssen and Bayer; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Sanofi, Pfizer, Eli Lilly, Amgen, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Janssen and Bayer; Financial Interests, Personal, Other, Support for attending meetings: MSD, BMS, Roche; Financial Interests, Personal, Advisory Board: Roche, MSD. Y. D'yachkova: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. T. Puri: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. A. Vickers: Financial Interests, Institutional, Other, AV is a full-time employee of RTI Health Solutions, an independent non-profit research organization, which was retained by Eli Lilly and Company to conduct the research which is the subject of this manuscript. Their compensation is unconnected to the studies on which they work: Eli Lilly and Company. S. Wolowacz: Financial Interests, Institutional, Sponsor/Funding, SW is a full-time employee of RTI Health Solutions, an independent non-profit research organization, which was retained by Eli Lilly and Company to conduct the research which is the subject of this manuscript. Their compensation is unconnected to the studies on which they work: Eli Lilly and Company. X. Wang: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. U. Kiiskinen: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company.
39P - Preliminary clinical investigations and mechanism exploration of furmonertinib in NSCLC with EGFR exon 20 insertion
- X. Zhang (Zhengzhou, China)
- X. Zhang (Zhengzhou, China)
- G. Feng (Tianjin, China)
- H. Han (Zhengzhou, China)
- B. Dong (Zhoukou, China)
- Y. Yang (Zhumadian, China)
- H. Zhu (Zhengzhou, China)
- S. Fan (Tianjin, China)
- H. Tang (Zhengzhou, China)
Abstract
Background
Here we analyzed the clinical efficacy of furmonertinib, a novel 3rd generation EGFR TKI, in advanced NSCLC patients (pts) who harboring EGFRex20ins and explored mechanism.
Methods
A retrospective single-arm analysis was performed to evaluate the efficacy of 20 NSCLC pts harboring EGFRex20ins receiving furmonertinib treatment from three institutions. Meanwhile, we investigated the clinical efficacy of furmonertinib versus osimertinib as second-line treatment, because pts about furmonertinib as first-line treatment were immature. In addition, the binding activity of different EGFR TKIs to EGFRex20ins were computationally constructed based on the crystal structure of EGFR_D770_N771insNPG/V948R (PDB ID: 7LGS) by the Schrödinger software (2021–2 Release).
Results
Of the 20 pts selected, we found that EGFRex20ins p.S768_D770dup (n = 5) variants were more common. Six first-line pts all achieved PR (ORR: 100%), five of the eight second-line pts achieved PR (ORR: 62.5%), and three of the six multiple-line pts achieved PR (ORR: 50.0%). We observed 14 pts with PR and six pts with SD as best response to furmonertinib (ORR: 70.0%, DCR: 100%). All pts showed tumor shrinkage in target lesions (median best percent change, −36.43% [−74.78%, −5.56%]). Median PFS was 10.2 (95% CI, 7.19–13.21) months (mo). Median DOR was 8.5 (95% CI, 4.97–12.03) mo. Comparative analysis of the efficacy of different groups showed that median PFS was significantly longer in furmonertinib group than in osimertinib (10.2 vs 3.8 mo, p = 0.008). Median OS was numerically longer in furmonertinib group than in osimertinib (18.9 vs 11.7 mo, p = 0.207). No grade 3 or above adverse events were observed. Furthermore, rather than erlotinib (GlideScore: −5.564; MM/GBSA: −52.8044), gefitinib (−7.68; −47.317), and afatinib (−5.075; −44.64), furmonertinib (−11.085; −68.1575) and osimertinib (−10.031; −63.87) revealed favorable binding activity to EGFRex20ins, with furmonertinib being the most significant.
Conclusions
Furmonertinib has positive clinical efficacy to advanced NSCLC pts with EGFRex20ins probably based on its favorable binding activity to EGFRex20ins. Furmonertinib may be the optimal choice for these pts in the future.
Legal entity responsible for the study
Hong Tang.
Funding
The Natural Science Foundation of Henan Province (No.212300410400).
Disclosure
All authors have declared no conflicts of interest.
40P - Updated data from the phase I Beamion Lung 1 trial of BI 1810631, a HER2 TKI, in patients (pts) with advanced solid tumours with HER2 aberrations
- F. Opdam (Amsterdam, Netherlands)
- F. Opdam (Amsterdam, Netherlands)
- J. Heymach (Houston, United States of America)
- M. Barve (Dallas, United States of America)
- H. Tu (Guangzhou, China)
- Y. Wu (Guangzhou, China)
- N. J. Gibson (Biberach, Germany)
- B. Sadrolhefazi (Ridgefield, United States of America)
- J. Serra (Barcelona, Spain)
- K. Yoh (Kashiwa, Japan)
- N. Yamamoto (Tokyo, Japan)
Abstract
Background
This ongoing phase Ia/Ib trial determines the safety, MTD, PK, PD and preliminary efficacy of BI 1810631 in pts with HER2 aberration-positive solid tumours.
Methods
Phase Ia: Pts with HER2 aberration-positive (overexpression, gene amplification/rearrangements or somatic mutation) advanced/unresectable/metastatic solid tumours refractory/unsuitable for standard therapy were enrolled. Pts received escalating doses of BI 1810631 BID (starting dose 15 mg) or BI 1810631 QD (starting dose 60 mg). Phase Ib will initially include 30 pts with advanced HER2 TK domain mutation-positive, pre-treated NSCLC. Primary endpoints: MTD based on number of DLTs; number of pts with DLTs (phase Ia); ORR (phase Ib). Secondary endpoints: number of pts with DLTs throughout entire treatment period and PK parameters (phase Ia/Ib); DoR, DCR, duration of disease control and PFS (phase Ib).
Results
As of 21 Dec 2022, 34 pts have been treated in the US, Netherlands, Japan and China. Pts had NSCLC (n = 21), colorectal cancer (n = 3), or other tumours (n = 10). Most pts had a pathological HER2 mutation (n = 25). Pts received BI 1810631 15, 30, 60, 100, 150 mg BID (n = 3/3/4/4/3) or 60, 120, 180, 240 mg QD (n = 5/4/5/3). Median number of cycles: 4 (range 1–14). Treatment ongoing: n = 23. To date, 3 DLTs has been observed (grade [G] 2 oedema [60 mg BID]; G3 anaemia [60 mg QD]; G3 elevated ALT [180 mg QD]). The MTD has not been reached with either schedule. Treatment-related adverse events (TRAEs) reported in 23 pts (68%). The most common TRAEs were diarrhoea (n = 9), anaemia (n = 5), increased alkaline phosphatase, increased ALT and hypoalbuminemia (all n = 4). Three pts had G3 TRAEs (anaemia/elevated GGT [n = 1]; increased ALT [n = 2]). In 29 pts evaluable for response the ORR (regardless of confirmation) was 34% (n = 10, all PRs; NSCLC: n = 8; oesophagus, cholangiocarcinoma: n = 1). The DCR was 90%. In 19 evaluable NSCLC pts the ORR was 42% and the DCR was 95%. Updated data will be presented at the meeting.
Conclusions
Preliminary data indicate that BI 1810631 is well tolerated and shows encouraging anti-tumour activity in pts with HER2 aberration-positive solid tumours. Phase Ia recruitment is ongoing.
Clinical trial identification
NCT04886804. Release date 14th May 2021.
Editorial acknowledgement
Medical writing support for the development of this poster, under the direction of the authors, was provided by Lynn Pritchard, of Ashfield MedComms, an Inizio Company, and funded by Boehringer Ingelheim.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
F. Opdam: Non-Financial Interests, Institutional, Other, Uncompensated Relationship: Boehringer Ingelheim, AstraZeneca/Merck, GlaxoSmithKline, Cytovation, InteRNA, Merus NV, Taiho Oncology, Pierre Fabre, Incyte. J. Heymach: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol-Myers Squibb, Spectrum Pharmaceuticals, Guardant Health, Hengrui Pharmaceutical, GlaxoSmithKline, EMD Serono, Takeda, Sanofi/Aventis, Genentech/Roche, Boehringer Ingelheim, Mirati Therapeutics, Janssen, Nexus Health Systems, Pneuma Respiratory; Financial Interests, Institutional, Advisory Role: Eli Lilly; Financial Interests, Personal, Speaker's Bureau: MJH Life Sciences; Financial Interests, Personal, Royalties, Licensing agreement between Spectrum and MD Anderson (including myself) regarding intellectual property for treatment of EGFR and HER2 exon 20 mutations: Licensing agreement between Spectrum and MD Anderson (including myself) regarding intellectual property for treatment of EGFR and HER2 exon 20 mutations; Financial Interests, Personal, Stocks/Shares: Cardinal Spine, Bio-Tree; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Spectrum Pharmaceuticals, GlaxoSmithKline. M. Barve: Financial Interests, Personal, Full or part-time Employment: Texas Oncology Physician Associates; Financial Interests, Personal, Stocks/Shares: Texas Oncology Physician Associates; Financial Interests, Personal, Research Grant: Mary Crowley Cancer Research. H. Tu: Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Eli Lilly, Roche, Pfizer, Boehringer Ingelheim. Y. Wu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Boehringer Ingelheim, Takeda, AstraZeneca, Eli Lilly, Roche, Pfizer, Boehringer Ingelheim, MSD Oncology, Bristol-Myers Squibb, Hengrui Pharmaceutical, BeiGene Beijing; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Roche, Pfizer, Bristol-Myers Squibb. N.J. Gibson: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. B. Sadrolhefazi: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J. Serra: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. K. Yoh: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Chugai Pharma, AstraZeneca, Eli Lilly Japan, Kirin Pharmaceuticals, Bristol-Myers Squibb Japan, Taiho Pharmaceutical, Janssen, Daiichi Sankyo/UCB Japan, Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Research Grant: Eli Lilly Japan, AstraZeneca, Pfizer, Taiho Pharmaceutical, Chugai Pharma, MSD, Takeda, Daiichi Sankyo, AbbVie. N. Yamamoto: Financial Interests, Personal, Speaker's Bureau: ONO, Chugai, Daiichi-Sankyo, Eisai; Financial Interests, Institutional, Research Grant: Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa Kirin, Takeda, ONO, Janssen Pharma, MSD, Merck, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, TORAY, KAKEN, AstraZeneca, Cmic; Financial Interests, Personal, Advisory Role: Eisai, Takeda, Otsuka, Boehringer Ingelheim, Cmic, Chugai, Merck, Healios.
41P - Efficacy of first-line (1L) nivolumab (N) + ipilimumab (I) by tumor histologic subtype in patients (pts) with metastatic nonsquamous NSCLC (mNSQ-NSCLC)
- H. Borghaei (Philadelphia, United States of America)
- H. Borghaei (Philadelphia, United States of America)
- D. Balli (Princeton, United States of America)
- L. Paz-Ares (Madrid, Spain)
- M. Reck (Grosshansdorf, Germany)
- S. S. Ramalingam (Atlanta, United States of America)
- J. R. Brahmer (Baltimore, United States of America)
- T. Ciuleanu (Cluj-Napoca, Romania)
- A. Pluzanski (Warsaw, Poland)
- J. Lee (Seongnam, Korea, Republic of)
- J. Gainor (Boston, United States of America)
- M. Schenker (Craiova, Romania)
- A. Schoenfeld (New York, United States of America)
- R. Bernabe Caro (Seville, Spain)
- N. Ready (Durham, United States of America)
- K. H. Lee (Cheongju, Korea, Republic of)
- B. Zurawski (Bydgoszcz, Poland)
- C. Audigier-Valette (Toulon, France)
- V. Baxi (Princeton, United States of America)
- W. Geese (Princeton, United States of America)
- K. J. O'Byrne (Brisbane, Australia)
Abstract
Background
Tumor histologic subtype (THS) has been reported to be a prognostic indicator for NSCLC; the solid subtype is associated with poor prognosis. 1L N + I has demonstrated durable, long-term clinical benefit vs chemotherapy (C) in pts with mNSCLC. Here we report exploratory analyses of overall survival (OS) with 1L N + I and association of biomarkers by mNSCLC THS using data from the CheckMate (CM) 227 and 568 trials.
Methods
THS was assessed in pts with evaluable mNSQ-NSCLC tissue in CM 227 Part 1 (NCT02477826; ph 3; N + I vs C; n = 675) and in CM 568 Part 1 (NCT02659059; ph 2; N + I, single arm; n = 170) by 3 independent pathologists using a modified version of the WHO NSCLC classification system. Samples were classified as solid, acinar, or other THS per consensus on the predominant THS. Exploratory assessments included OS, tumor PD-L1, TMB, select somatic mutations (muts; TP53, KRAS, and STK11; FoundationOne CDx™), and gene expression analysis (GEA) by THS.
Results
Baseline characteristics were generally consistent across THS and treatment groups. Minimum follow-up was 61.3 and 61.2 mo in CM 227 and 568, respectively. In both trials, greater OS benefit was observed in N + I-treated pts with solid vs acinar THS (CM 227: HR 0.60, 95% CI 0.45–0.80; CM 568: HR 0.67, 95% CI 0.44–1.02; table). In contrast, among C-treated pts, OS was similar in pts with solid or acinar THS in CM 227 (HR 1.01, 95% CI 0.77–1.32). Further exploratory analysis identified a trend toward higher tumor PD-L1 expression and TMB in pts with solid vs acinar THS (table). A higher frequency of TP53 muts and lower frequencies of KRAS and STK11 muts were also observed in the solid THS. These results and findings from GEA by THS will be presented.
Biomarkers and OS by THS
| CM 227 Part 1 | CM 568 Part 1 | |||
|---|---|---|---|---|
| Solid (n = 192) | Acinar (n = 91) | Solid (n = 77) | Acinar (n = 48) | |
| Median tumor PD-L1 expression, % (range) | 50 (0–100) | 1 (0–100) | 30 (0–100) | 0 (0–80) |
| Median TMB, mut/Mb (range) | 8.8 (0–66.8) | 6.3 (0–44.1) | 10.1 (1.3–98.4) | 5.7 (1.3–17.6) |
| OS | ||||
| Median, mo (95% CI) | 18.7 (13.5–28.4) | 13.3 (10.0–17.1) | 26.5 (14.6–47.3) | 12.9 (8.6–24.0) |
| HR, solid vs acinar (95% CI) | 0.60 (0.45–0.80) | – | 0.67 (0.44–1.02) | – |
| 5-y rate, % (95% CI) | 31.0 (24.9–38.4) | 6.0 (2.6–14.0) | 31.1 (21.9–44.1) | 18.4 (9.9–34.3) |
THS-evaluable pts: CM 227 (N + I and C), 675 pts and CM 568 (N + I), 170 pts; solid, 59% and 45%; acinar, 26% and 28%; other, 10% and 7%; not specified, 5% and 19%, respectively.
Conclusions
Greater long-term OS benefit with N + I was seen in pts with the solid mNSCLC THS, a subgroup with poor prognosis, vs pts with the acinar THS. Exploratory PD-L1, TMB, and mut analysis may provide insight into the clinical benefit of 1L dual immunotherapy by THS.
Clinical trial identification
NCT02477826, NCT02659059.
Editorial acknowledgement
Medical writing and editorial support for the development of this abstract, under the direction of the authors, was provided by Wendy Sacks, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
H. Borghaei: Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Eli Lilly, Amgen; Financial Interests, Personal, Other, consulting fees: BMS, Eli Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Amgen, Axiom, PharmaMar, Takeda, Mirati, Daiichi Sankyo, Guardant, Natera, Oncocyte, BeiGene, iTEO, Jazz Pharmaceuticals, Janssen, Da Volterra; Financial Interests, Personal, Other, honoraria: Amgen, Pfizer, Daiichi Sankyo, Regeneron; Financial Interests, Personal, Other, support for attending meetings and travel: Amgen, BMS, Merck, Eli Lilly, EMD-Serono, Genentech, Regeneron; Financial Interests, Personal, Advisory Board: University of Pennsylvania: CAR T Program, Takeda, Incyte, Novartis; Financial Interests, Personal, Stocks/Shares: Sonnetbio (Stock Options); Inspirna (formerly Rgenix, Stock Options); Nucleai (stock options); Financial Interests, Personal, Writing Engagements, medical writing: BMS, Amgen, AstraZeneca. D. Balli: Financial Interests, Personal, Other, Support for attending meetings and travel. Patents planned, issued, or pending.: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AstraZeneca, Eli Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-Cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Eli Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President.ASEICA(Spanish Association of Cancer Research): ASEICA; Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Novartis, Merck, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Mirati, Pfizer, Sanofi, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, MSD, Roche. S.S. Ramalingam: Financial Interests, Personal, Other, Editor in Chief, Cancer journal: American Cancer Society; Financial Interests, Personal, Research Grant: Merck, AstraZeneca, Advaxis, BMS, Amgen, Takeda, Genmab, GSK. J.R. Brahmer: Financial Interests, Personal, Writing Engagements, medical writing: Bristol Myers Squibb, Merck; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Other, personal payment: Bristol Myers Squibb, AstraZeneca, Merck, Regeneron; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Johnson and Johnson, Sanofi, GlaxoSmithKline, Society for the Immunotherapy of Cancer, LUNGevity Lung Cancer Research Foundation, Lung Cancer Foundation of America. T. Ciuleanu: Financial Interests, Institutional, Other, Principal Investigator: Jounce Therapeutics. A. Pluzanski: Financial Interests, Personal, Other, consulting fees: BMS, MSD; Financial Interests, Personal, Invited Speaker: BMS, MSD, Roche; Financial Interests, Personal, Other, support for attending meetings and travel: BMS, MSD; Financial Interests, Personal, Advisory Board: BMS. J. Gainor: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb, Merck, Genentech/Roche, Takeda, Eli Lilly, Moderna, AstraZeneca, Pfizer, Novartis, iTeos, Karyopharm, Silverback Therapeutics, GlydeBio, BeiGene; Financial Interests, Personal, Stocks/Shares, Immediate family member is an employee. Note: Ironwood Pharmaceuticals is not involved in any oncology drug development. It is focused on gastroenterology.: Ironwood Pharmaceuticals; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Moderna, Jounce, Alexo. M. Schenker: Financial Interests, Personal and Institutional, Invited Speaker, Payment for Clinical trials activities: B.M.S., M.S.D., Roche, Merck Serono, Sanofi, Regeneron, AstraZeneca, Pfizer, G.S.K,, Novartis, Astellas, Pharma Mar, BeiGene, Clovis Pharmaceutical, AbbVie, Bioven, Mylan, Samsung Pharmaceutical, Eisai, Gilead, Amgen, Daiichi Sankyo. A. Schoenfeld: Financial Interests, Personal, Advisory Role, consulting and advisory role: J&J, KSQ therapeutics, BMS, Merck, Enara Bio, Perceptive Advisors, Oppenheimer and Co, Umoja Biopharma, Legend Biotech, Iovance Biotherapeutics, Lyell Immunopharma and Heat Biologics. Research funding: GSK (Inst), PACT pharma (Inst), Iovance Biotherapeuti. R. Bernabe Caro: Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Speaker's Bureau: Roche, BMS, Pfizer, MSD, Amgen, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Takeda, Roche, BMS, AstraZeneca. N. Ready: Financial Interests, Personal, Advisory Role, consulting fees: Merch, Jazz Pharmaceuticals, BMS, Amgen; Financial Interests, Personal, Invited Speaker: BMS, Jazz Pharmaceuticals. K.H. Lee: Financial Interests, Personal, Advisory Board: BMS, MSD, Eli Lilly, Yuhan, Pfizer, AstraZeneca; Financial Interests, Personal, Funding: Merck. B. Zurawski: Financial Interests, Personal, Funding, personal fees: Amgen, AstraZeneca, BMS, GSK, Janssen-Cilag, MSD, Roche. V. Baxi: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Member of the Board of Directors: Digital Pathology Association; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. W. Geese: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. K.J. O'Byrne: Financial Interests, Personal, Other, Advisor/consultant on project development by the company: TriStar; Financial Interests, Personal, Other, Invited speaker; advisory board: BMS; Financial Interests, Personal, Other, Advisory board; invited speaker: AstraZeneca, MSD, Janssen; Financial Interests, Personal, Other, advisory board; invited speaker: Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Takeda; Financial Interests, Personal, Other, Advisory board: Pfizer; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board, Advice on development of Lasertinib: Yuhan; Financial Interests, Personal, Advisory Board, Advice re cabozantinib: Ipsen; Financial Interests, Personal, Advisory Board, Advice of drug development program: BeiGene; Financial Interests, Personal, Invited Speaker, Topic - Tepotinib: Merck; Financial Interests, Personal, Other, Sponsorship for travel, accommodation and registration for ESMO Congress, Paris, 2022: Bayer; Financial Interests, Personal, Stocks/Shares, 5% non-dilutable shares in a start-up Pharma company: RepLuca Pharmaceuticals Pty Ltd; Financial Interests, Personal, Stocks/Shares, Start-up diagnostics focused on genomics: DGC diagnostics; Financial Interests, Personal, Other, Co-founder, board member and share holder (15%) in the Pharma and biotech company: Carpe Vitae Pharmaceuticals Pty Ltd; Financial Interests, Personal, Invited Speaker, Steering committee member 2 trials- CA-209-227- CA-224-095: BMS; Financial Interests, Personal, Invited Speaker, Steering Committee member LUX-Lung program: Boehringer Ingelheim; Non-Financial Interests, Personal, Other, Chair an education session: foundation medicine. All other authors have declared no conflicts of interest.
42P - Pembrolizumab vs chemotherapy in Chinese patients with non-small cell lung cancer (NSCLC) and PD-L1 TPS ≥1%: 5-year update from KEYNOTE-042
- Y. Wu (Guangzhou, China)
- Y. Wu (Guangzhou, China)
- L. Zhang (Beijing, China)
- Y. Fan (Hangzhou, China)
- J. Zhou (Hangzhou, China)
- L. Zhang (Guangzhou, China)
- Q. Zhou (Guangzhou, China)
- W. Li (Changchun, China)
- C. Hu (Changsha Hunan, China)
- G. Chen (Harbin, China)
- X. Zhang (Shanghai, China)
- C. Zhou (Shanghai, China)
- C. Arenas (Madrid, Spain)
- Z. Chen (Beijing, China)
- W. Yu (Beijing, China)
- T. Mok (Shatin, Hong Kong Special Administrative Region, China)
Abstract
Background
After 4 y of follow-up in patients (pts) enrolled in China in the phase III KEYNOTE-042 study, pembrolizumab (pembro) improved OS vs chemotherapy (chemo) in pts with previously untreated advanced or metastatic NSCLC without EGFR/ALK alterations in the PD-L1 tumor proportion score (TPS) ≥50% (HR, 0.66; 95% CI, 0.45–0.95), ≥20% (0.68, 0.49–0.93), and ≥1% (0.67, 0.51–0.89) groups. We report results after 16 mo of additional follow-up.
Methods
Eligible pts were randomized 1:1 to receive pembro 200 mg Q3W for ≤35 cycles or carboplatin + paclitaxel or pemetrexed with optional pemetrexed maintenance (nonsquamous only). Primary endpoints were OS in pts with PD-L1 TPS ≥50%, ≥20%, and ≥1%. No alpha was assigned to this exploratory analysis of pts enrolled in China in KEYNOTE-042 global (NCT02220894) and China extension (NCT03850444) studies.
Results
Of 262 pts enrolled in China, 128 were randomized to pembro and 134 to chemo. Median time from randomization to database cutoff (Sep 12, 2022) was 63.7 (range, 56.3–72.6) mo. Pembro prolonged OS vs chemo in pts with PD-L1 TPS ≥50% (HR 0.65, 95% CI 0.45–0.93), ≥20% (0.67, 0.49–0.91), and ≥1% (0.66, 0.51–0.87). 5-y OS rates were ∼2 fold higher with pembro vs chemo across all 3 PD-L1 TPS groups (table). Grade 3–5 treatment-related AEs occurred in 19.5% of pts in the pembro arm and 68.8% in the chemo arm. Of 22 pts who completed 35 cycles of pembro, ORR was 81.8% (95% CI, 59.7%–94.8%) and 3-y OS rate after completion of 35 cycles (∼5 y after randomization) was 56.6%. At data cutoff, 80 pts in the pembro arm and 79 in the chemo arm had begun subsequent therapy; 5 pts began second-course pembro.
| PD-L1 TPS ≥50% | PD-L1 TPS ≥20% | PD-L1 TPS ≥1% | ||||
|---|---|---|---|---|---|---|
| Pembro n = 72 | Chemo n = 74 | Pembro n = 101 | Chemo n = 103 | Pembro n = 128 | Chemo n = 134 | |
| OS, median (95% CI), mo | 24.5 (17.4–34.3) | 13.8 (10.1–18.3) | 21.9 (17.4–27.0) | 13.5 (10.1–17.9) | 20.2 (17.4–25.3) | 13.5 (10.1–17.9) |
| OS HR (95% CI) | 0.65 (0.45–0.93) | 0.67 (0.49–0.91) | 0.66 (0.51–0.87) | |||
| 5-y OS rate (95% CI), % | 18.4 (10.2–28.5) | 8.3 (3.3–16.2) | 19.1 (12.0–27.5) | 10.2 (5.2–17.1) | 19.0 (12.6–26.4) | 9.5 (5.2–15.5) |
| ORR (95% CI), % | 41.7 (30.2–53.9) | 24.3 (15.1–35.7) | 34.7 (25.5–44.8) | 24.3 (16.4–33.7) | 32.0 (24.1–40.9) | 24.6 (17.6–32.8) |
| DOR, median (range), mo | 16.5 (1.4+ to 64.1+) | 11.7 (1.6+ to 63.4+) | 16.5 (1.4+ to 64.1+) | 10.9 (1.6+ to 63.4+) | 16.0 (1.4+ to 64.1+) | 10.9 (1.1+ to 63.4+) |
Conclusions
Similar to the global KEYNOTE-042 study, after 5 y of follow-up, pembro continued to demonstrate improved OS vs chemo with manageable safety in Chinese pts with previously untreated advanced or metastatic NSCLC without EGFR/ALK alterations with PD-L1 TPS ≥1%. These data further support pembro monotherapy as a standard of care for these pts.
Clinical trial identification
NCT02220894 and NCT03850444.
Editorial acknowledgement
Writing support was provided by Kathleen Estes, PhD, of ICON plc (Blue Bell, PA, USA), funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
Y. Wu: Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Novartis, Takeda, MSD; Financial Interests, Personal, Other, Honorarium: AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sanofi (all not promotional activities). L. Zhang: Financial Interests, Personal, Research Grant: Hengrui, BMS, and Innovent Biologics. Q. Zhou: Financial Interests, Personal, Other, Lecture and presentations fees to myself: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi outside the submitted work. C. Zhou: Financial Interests, Personal, Other, honoraria: Boehringer Ingelheim, Eli Lilly, Hengrui, MSD, Sanofi, F. Hoffmann-La Roche Ltd., and Qilu. C.G. Arenas: Financial Interests, Personal, Full or part-time Employment: MSD Spain; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. Z. Chen: Financial Interests, Personal, Full or part-time Employment: MSD China. W.C. Yu: Financial Interests, Personal, Full or part-time Employment: MSD China. T.S.K. Mok: Financial Interests, Personal, Research Grant: AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, and XCovery; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Bristol Myers Squibb, Taiho, and Takeda Oncology; Financial Interests, Personal, Other, honoraria: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Bristol Myers Squibb, OncoGe; Financial Interests, Personal, Stocks/Shares: Sanomics Ltd.; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Merck Serono, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceutical. All other authors have declared no conflicts of interest.
43P - Camrelizumab plus famitinib as first-line treatment in advanced NSCLC patients with PD-L1 TPS ≥1%: A report from a multicenter, open-label, phase II basket trial
- S. Ren (Shanghai, China)
- S. Ren (Shanghai, China)
- X. Wang (Guangzhou, China)
- B. Han (Shanghai, China)
- Y. Pan (Hefei, China)
- J. Zhao (Beijing, China)
- Y. Cheng (Jinan, China)
- S. Hu (Wuhan, China)
- T. Liu (Shanghai, China)
- Y. Li (Chengdu, China)
- Y. Cheng (Changchun, China)
- J. Feng (Nanjing, China)
- S. Yi (Zhengzhou, China)
- S. Gu (Changsha, China)
- S. Gao (Luoyang, China)
- Y. Luo (Changsha, China)
- Y. Liu (Zhengzhou, China)
- C. Liu (Shenyang, China)
- H. Duan (Shanghai, China)
- C. Zhou (Shanghai, China)
- J. Fan (Shanghai, China)
Abstract
Background
The combination of immune-checkpoint inhibitors and antiangiogenic agents can modulate the microenvironment in a synergistic manner and represents a promising treatment option for NSCLC. The efficacy and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (a receptor tyrosine kinase inhibitor) as first-line therapy for advanced NSCLC with PD-L1 TPS ≥1% was explored in an open-label, multicenter, phase II basket trial.
Methods
Eligible patients (pts) received camrelizumab (200 mg once every 3 weeks by intravenous infusion) plus oral famitinib (20 mg once daily). Primary endpoint was confirmed objective response rate (ORR) assessed by investigator per RECIST v1.1. Disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS), 6-, 9-, 12-month OS rates and safety profile were secondary endpoints.
Results
Among all enrolled 41 pts, 21 (51.2%) had PD-L1 TPS 1–49% and 20 (48.8%) had PD-L1 TPS ≥50% per local laboratory testing. As of data cutoff on Jun 22, 2022, 22 (53.7%) pts had achieved a confirmed objective response. This combination regimen achieved an ORR of 53.7% (95% confidence interval [CI], 37.4–69.3), and the DCR was 92.7% (95% CI, 80.1–98.5). Median DoR had not been reached yet and the median TTR was 2.1 mos (range, 1.4–8.3). With the median follow-up duration of 12.5 mos (range, 1.0–24.2), the median PFS was 16.6 mos (95% CI, 8.3-NR), median OS was 20.4 mos (95% CI, 20.4-NR; data not mature), and the estimated 12-month OS rate was 76.8% (95% CI, 60.0–87.3), respectively. The most common ≥ grade 3 treatment-related adverse events were hypertension (22.0%), increased alanine aminotransferase (12.2%) and decreased neutrophil count (9.8%). One patient (2.4%) died from grade 5 hemoptysis, which the investigator considered possibly related to the study treatment.
Conclusions
Camrelizumab plus famitinib exhibited encouraging antitumor activity in advanced NSCLC pts whose tumor expressed PD-L1 TPS ≥1% with an acceptable safety profile. In this patient population, this combination regimen might offer an alternative treatment strategy that deserves further investigation.
Clinical trial identification
NCT04346381.
Editorial acknowledgement
Medical writing support was provided by Lin Dong (Hengrui Pharmaceuticals).
Legal entity responsible for the study
Jiangsu Hengrui Pharmaceuticals Co., Ltd.
Funding
Jiangsu Hengrui Pharmaceuticals Co., Ltd.
Disclosure
H. Duan: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd. All other authors have declared no conflicts of interest.
44P - Dostarlimab (Dos) or pembrolizumab (Pem) + chemotherapy (CT) in previously untreated metastatic non-squamous non-small cell lung cancer (NSCLC): Patient (Pt) and disease characteristics subgroup analyses from the PERLA trial
- A. O. Ortega Granados (Jaén, Spain)
- A. O. Ortega Granados (Jaén, Spain)
- S. Lim (Seoul, Korea, Republic of)
- M. Schenker (Craiova, Romania)
- F. De Marinis (Milan, Italy)
- J. Puig (San Juan, Argentina)
- D. Lee (Seoul, Korea, Republic of)
- E. Arriola (Barcelona, Spain)
- J. Fuentes Pradera (Seville, Spain)
- S. O'Donnell (Collegeville, United States of America)
- Z. Szijgyarto (Stevenage, United Kingdom)
- L. Cho (Collegeville, United States of America)
- J. Ahn (Seoul, Korea, Republic of)
Abstract
Background
The randomized, double-blind phase II PERLA trial was the first global head-to-head comparison of 2 programmed death (PD)-1 inhibitors in NSCLC and showed similar efficacy for Dos + CT and Pem + CT with no new safety signals identified. Here, we report overall response rate (ORR) by pt and disease characteristics.
Methods
PERLA evaluated efficacy of Dos + CT and Pem + CT as first-line treatment for pts with metastatic non-squamous NSCLC, no targetable oncogenic drivers, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1. Pts, stratified by PD-L1 and smoking status, were randomized 1:1 to Dos 500 mg or Pem 200 mg every 3 weeks (Q3W) for ≤35 cycles, both combined with ≤35 cycles of 500 mg/m2 pemetrexed and ≤4 cycles of platinum-based chemotherapy (area under curve5 mg/mL/min carboplatin or 75 mg/m2 cisplatin) Q3W. Disease assessments were at Week (W) 6 and 12, then every 9Ws until W48, then every 12Ws. ORR by pt and disease characteristics were exploratory analyses; point estimates and 95% Clopper–Pearson confidence intervals (CIs) were assessed.
Results
ORR by pt and disease characteristic subgroups are shown in the table. ORR was similar across subgroups and numerically favoured Dos + CT in all but those with ECOG PS 0, in which it was 46% for both treatment groups. ORR remained the same within Dos + CT regardless of age or ECOG PS (46%); however, ORR was lower in patients treated with Pem + CT who had ECOG PS 1 as opposed to 0.
ORR by pt/disease characteristics
| ORR, | Dos + CT (N = 121) | Pem + CT (N = 122) |
|---|---|---|
| Age | - | - |
| <65 years | 46 (33.7–59.0), 30/65 | 35 (22.9–48.9), 20/57 |
| ≥65 years | 46 (33.0–60.3), 26/56 | 38 (26.7–51.4), 25/65 |
| Sex | - | - |
| Female | 42 (25.5–59.2), 15/36 | 33 (20.0–49.0), 15/45 |
| Male | 48 (37.3–59.3), 41/85 | 39 (28.0–50.8), 30/77 |
| ECOG PS | - | - |
| 0 | 46 (29.5–63.1), 17/37 | 46 (31.8–60.7), 23/50 |
| 1 | 46 (35.5–57.6), 39/84 | 31 (20.2–42.5), 22/72 |
| Brain metastasis | - | - |
| Yes | 50 (28.2–71.8), 11/22 | 27 (7.8–55.1), 4/15 |
| No | 45 (35.4–55.8), 45/99 | 38 (29.1–48.2), 41/107 |
| Platinum-based chemotherapy | - | - |
| Cisplatin | 41 (20.7–63.6), 9/22 | 36 (12.8–64.9), 5/14 |
| Carboplatin | 47 (37.3–57.8), 47/99 | 37 (27.9–46.9), 40/108 |
by blinded independent central review per RECIST v1.1.
Conclusions
ORR was similar between treatments and subgroups. In addition to the similar efficacy between treatments and tolerable safety profile, reported previously for PERLA, these results support further investigation of Dos in combination with other therapies.
Clinical trial identification
NCT04581824.
Editorial acknowledgement
Editorial support was provided by Eva Kane, PhD, of Fishawack Health, and funded by GSK.
Legal entity responsible for the study
GSK.
Funding
This study was funded by GSK (213403).
Disclosure
A.L.O. Ortega Granados: Financial Interests, Personal, Full or part-time Employment: Servicio Andaluz de Salud; Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme. S.M. Lim: Financial Interests, Personal, Research Grant: Yuhan, Janssen; Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Takeda, J Ints Bio, BMS; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, GSK, Roche, Hengrui, BridgeBio Therapeutics, Oscotec, Daiichi Sankyo. M. Schenker: Financial Interests, Personal and Institutional, Funding, Funding for clinical trial activities.: GSK, BMS, MSD, Roche, AstraZeneca, Merck Serono, Astellas, Amgen, Bayer, BeiGene, Clovis, Gilead, Eli Lilly, Pfizer, Novartis, Sanofi, PharmaMar, AbbVie, Regeneron, Mylan, Samsung Pharmaceuticals, Bioven, Eisai, Five Prime, Daiichi Sankyo. F. de Marinis: Financial Interests, Personal, Speaker's Bureau: Merck, GSK, Roche, Bristol Myers Squibb, AstraZeneca, Novartis; Financial Interests, Personal, Advisory Board: Merck, GSK, Roche, Bristol Myers Squibb, AstraZeneca, Novartis. J.M. Puig: Financial Interests, Institutional, Principal Investigator: CER San Juan, centro polivalente de asistencia e Investigación clinica. D.H. Lee: Financial Interests, Personal, Other, Personal fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, CJ Healthcare, Eli Lilly, ChongKeunDang, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, ST Cube, AbbVie, Takeda, Menarini, BC Pharma, Yuhan; Non-Financial Interests, Personal, Other: Takeda, Blueprint Medicine. E. Arriola: Financial Interests, Personal, Advisory Role: BMS, Roche, MSD, Pfizer, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Invited Speaker: BMS, Roche, MSD, Pfizer, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Research Grant: Roche, Pfizer; Financial Interests, Institutional, Funding: BMS, Roche, Pfizer; Financial Interests, Personal, Other, Travel and educational expenses: BMS, MSD, Roche, Eli Lilly; Financial Interests, Personal, Ownership Interest: TrialingHealth S.L. J. Fuentes Pradera: Financial Interests, Personal and Institutional, Principal Investigator: Roche, MSD, AstraZeneca, Pfizer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Sanofi, Takeda. Z. Szijgyarto: Financial Interests, Institutional, Full or part-time Employment: GSK; Financial Interests, Institutional, Stocks/Shares: GSK. L. Cho: Financial Interests, Institutional, Full or part-time Employment: GSK; Financial Interests, Institutional, Stocks/Shares: GSK. J.S. Ahn: Financial Interests, Personal, Invited Speaker: Roche Korea, Menarini Korea, Pfizer, Boehringer Ingelheim, Kyowa Kirin, Amgen Korea, Yuhan, AstraZeneca Korea, Bayer Korea, Takeda Phar, Novartis Korea, Hanmi, BC World; Financial Interests, Personal, Advisory Role: Immuneoncia, Pharmbio Korea, Yooyoung, Vifor Pharma, Bixink. All other authors have declared no conflicts of interest.
45P - DCVAC/LuCa with chemotherapy in patients with stage IV, non-squamous NSCLC without EGFR/ALK aberrations: Five-year survival update
- X. Ling (Shanghai, China)
- X. Ling (Shanghai, China)
- R. Zhong (Shanghai, China)
- S. Cao (Shanghai, China)
- L. Zhang (Shanghai, China)
- J. Xu (Shanghai, China)
- B. Zhang (Shanghai, China)
- X. Zhang (Shanghai, China)
- H. Wang (Shanghai, China)
- B. Han (Shanghai, China)
- H. Zhong (Shanghai, China)
Abstract
Background
Our study was the first clinical trial showing the safety and efficacy of DCVAC/LuCa (dendritic cell vaccines for lung cancer) combined with chemo in Chinese NSCLC patients (Zhong R, Ling X, et al. ESMO Open 2022). The OS data was not mature in our last report. Here, we present a survival update based on 33 months of additional follow-up.
Methods
Patients with stage IV, non-squamous NSCLC, no known EGFR/ALK aberrations, and who had not received systemic therapy for NSCLC prior to treatment, were enrolled in this study. Patients were treated with carboplatin/pemetrexed for up to 6 cycles, followed by pemetrexed maintenance for up to 21 cycles. Non-progression patients after two cycles of chemotherapy, assessed as mITT population, received DCVAC/LuCa subcutaneously (s.c.) on day 15 of cycle 3, and thereafter q3w (day 15 of chemotherapy cycles) for up to 15 doses. The dose of DCVAC/LuCa s.c. depended on the baseline number of leucocytes of each patient.
Results
A total of 61 patients were enrolled. At the clinical cutoff date (14 Dec 2022), the median follow-up was 64 months. In the mITT population (n = 44), the median OS was 27.4 months (95% CI, 18.1 to 36.7 months), the 3-year OS rate was 37.2% and the 5-year OS rate was 23.4%. Among the 15 patients who completed 15 cycles of DC vaccination, 6 (40%) remained alive at a 5-year follow-up. Patients who received higher-dose DCVAC/LuCa had a better prognosis than patients who received lower-dose DCVAC/LuCa.
Conclusions
The combination of DCVAC/LuCa and chemo continued to provide long-term benefits as a first-line treatment in Chinese patients with stage IV, non-squamous NSCLC without EGFR/ALK aberrations. The long-term benefits and the good safety profile support the conduct of a validation trial in a larger population with greater diversity.
Legal entity responsible for the study
SOTIO Medical Research (Beijing) Co., Ltd.
Funding
SOTIO Medical Research (Beijing) Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.
46P - Multi-center, phase II study of docetaxel (DTX) plus ramucirumab (RAM) following platinum-based chemotherapy plus ICIs in patients with NSCLC: SCORPION study
- R. Matsuzawa (Nagoya, Japan)
- R. Matsuzawa (Nagoya, Japan)
- M. Morise (Nagoya, Japan)
- K. Ito (Matsusaka, Japan)
- O. Hataji (Matsusaka, Japan)
- K. Takahashi (Anjo, Japan)
- Y. Kuwatsuka (Nagoya, Japan)
- Y. Goto (Toyoake, Japan)
- K. Imaizumi (Toyoake, Japan)
- H. Itani (Ise, Japan)
- T. Yamaguchi (Nagoya, Japan)
- Y. Zenke (Kashiwa, Japan)
- M. Oki (Nagoya, Japan)
- M. Ishii (Nagoya, Japan)
Abstract
Background
Platinum-based chemotherapy plus immune check point inhibitors (ICIs) have become a front-line standard treatment in NSCLC, but no prospective data of DTX plus RAM following front-line chemotherapy plus ICIs are available. Previous research has proven residual ICIs efficacy beyond 20 weeks after termination of ICIs, and VEGF-R2 blockade could enhance antitumor immunity by improving T-cell function. Here, we report the results of multicenter, phase II study of DTX plus RAM following front-line chemotherapy plus ICIs.
Methods
The primary end point of the study was objective response rate (ORR), and secondary endpoints were disease control rate (DCR), progression-free survival (PFS), and safety etc. Patients were treated with 60 mg/m2 of DTX and 10 mg/kg of RAM on day 1 with strong recommendation of pegfilgrastim on day 2 every 3 weeks. A null and alternative hypothesis of ORR were set as 10% and 30% with α error of 0.1 and β error of 0.1.
Results
Thirty-three patients were recruited from 8 institutions. Patient characteristics were as follows: median age (range): 66 (42–79) y; ECOG-PS 1, n = 13 (39%); interval after last administration of ICIs<6 weeks, n = 21 (64%). In the efficacy analysis population (n = 32), the primary endpoint was met as 11 patients achieved PR with ORR at 34.4% (80%CI, 23.1–47.2%). Another 15 patients achieved SD and the DCR was 81.3% (95%CI, 63.6–92.8%). Median PFS was 6.5 months. Grade≥3 anemia and febrile neutropenia was observed in 2 (6%) and 3 patients (9%). No treatment-related deaths and no new safety signals were observed.
Conclusions
DTX plus RAM demonstrated encouraging antitumor activity with a manageable safety profile in patients who have failed with front-line chemotherapy plus ICIs.
Clinical trial identification
jCRTs041190077.
Legal entity responsible for the study
M. Morise.
Funding
Eli Lilly.
Disclosure
M. Morise: Financial Interests, Institutional, Research Grant: Eli Lilly, Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator: Roche, Chugai, AstraZeneca, Taiho, Merck Serono, AbbVie, Ono. K. Ito: Financial Interests, Personal, Invited Speaker: Eli Lilly. All other authors have declared no conflicts of interest.
47P - Timing of radiotherapy affects outcomes of patients with metastatic NSCLC who receive immunotherapy
- S. Li (Jacksonville, United States of America)
- S. Li (Jacksonville, United States of America)
- J. Inampudi (Jacksonville, United States of America)
- H. Koshiya (Jacksonville, United States of America)
- J. Patel (Jacksonville, United States of America)
- N. Wiest (Jacksonville, United States of America)
- T. Pai (Jacksonville, United States of America)
- E. Butts (Jacksonville, United States of America)
- B. McKinley (Jacksonville, United States of America)
- J. Wang (Jacksonville, United States of America)
- G. Sacchi de Camargo Correia (Jacksonville, United States of America)
- O. Mosalem (Jacksonville, United States of America)
- R. Manochakian (Jacksonville, United States of America)
- Y. Zhao (Jacksonville, United States of America)
- Y. Lou (Jacksonville, United States of America)
Abstract
Background
Radiotherapy (RT) and immunotherapy (IO) may have synergistic anti-tumor effect for treating metastatic non-small-cell lung cancer (mNSCLC). However, the optimal timing of RT in relevance to IO and whether it affects outcomes is unknown.
Methods
We conducted a retrospective study of all patients with mNSCLC treated with IO at our institution (2011–2022). Patients who received targeted therapy or prior concurrent chemoRT + durvalumab were excluded.
Results
In this cohort of 225 patients, 56% were male, 82% were Caucasian. The median age was 68 (44–95). The histology was predominantly adenocarcinoma (79%). The most common metastatic sites were bone (41%) followed by CNS (25%). 56% patients received RT before or during IO. 27% never received RT. 17% received RT after discontinuation of IO. Pembrolizumab was the most used IO (78%), followed by Nivolumab (14%) and Atezolizumab (12%). Most patients received IO in the frontline (60%). We observed no statistical difference in PFS, OS, or development of immune-related adverse events in patients who received RT before or during IO compared to patients without RT (PFS: 5.9 vs. 5.5 months, p = 0.66; OS: 16.9 vs. 13.1 months, p = 0.84; irAE: 26.2% vs. 34.4%, p = 0.24). Patients with RT were divided into four groups by the timing of RT related to IO: >12 months prior to IO (N = 29), between 1 and 12 months prior to IO (N = 39), <1 month prior to IO (N = 30), after IO initiation (N = 28). The median PFS (months) of the above groups were 4.3, 12.6, 4.2, and 5.1, respectively, and the median OS (months) were 16.5, 25, 13.9, and 16, respectively. We found significantly higher PFS in patients who received RT between 1 and 12 months before IO, compared with those received RT<1 month before IO (12.6 vs. 4.2 months, p = 0.005, HR 0.46, 95% CI 0.26–0.83), or compared with patients without RT (12.6 vs. 5.5 months, p = 0.0197, HR 0.56, 95% CI 0.36–0.89). This trend was sustained in the OS analysis (25 vs. 13.9 months, p = 0.08; 25 vs. 13.1 months, p = 0.18).
Conclusions
We observed statistically significant and clinically meaningful PFS benefits of IO in patients with mNSCLC who received RT between 1 and 12 months prior to IO. There is a positive trend for OS benefit, although not statistically significant. These findings need to be verified in a larger cohort.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
48P - Characteristics and treatment patterns of patients with advanced or metastatic non-small cell lung cancer managed with first-line immuno-oncology strategies in Greece: Interim results of a real-world prospective study (IO-HORIZON)
- H. Linardou (Athens, Greece)
- H. Linardou (Athens, Greece)
- A. Charpidou (Athens, Greece)
- A. Koumarianou (Haidari, Greece)
- G. Mountzios (Athens, Greece)
- P. A. Kosmidis (Marousi, Greece)
- C. Christodoulou (Athens, Greece)
- D. Mavroudis (Heraklion, Greece)
- A. N. Christopoulou (Patras, Greece)
- I. Korantzis (Thessaloniki, Greece)
- S. Baka (Thessaloniki, Greece)
- M. Vaslamatzis (Athens, Greece)
- I. Athanasiadis (Marousi, Greece)
- A. Koutras (Patras, Greece)
- D. Mauri (Ioannina, Greece)
- A. Kotsakis (Larissa, Greece)
- D. Ziogas (Athens, Greece)
- A. Desiniotis (Athens, Greece)
- I. Dimitriadis (Athens, Greece)
- K. Syrigos (Athens, Greece)
Abstract
Background
IO-HORIZON aims to provide real-world evidence (RWE) on the profile and treatment patterns of patients with advanced/metastatic non-small cell lung cancer (NSCLC) receiving first-line (1L) immuno-oncology (IO) treatment in routine settings in Greece.
Methods
This is an ongoing, non-interventional, prospective study in adults with stage IIIB-IV NSCLC receiving 1L approved IO treatment. Data are collected during routine clinic visits. Baseline results after accrual completion are presented.
Results
From May/2020 to Nov/2021, 240 eligible Caucasian patients (75.4% male, 91.3% ever-smokers) were enrolled by 17 oncology clinics (7 private, 10 public) in Greece. At 1L IO initiation, patients’ median age was 69.0 years, with a median of 2.0 months elapsed since advanced/metastatic disease diagnosis. ECOG performance status was 0/1/2 in 62.5/31.3/6.3%. Disease stage was IIIB/IIIC/IV in 5.0/2.1/92.9%; of the latter patients, 78.5% had de novo stage IV, 23.3% ≥3 metastatic sites, while 36.8% had bone, 17.9% brain, and 16.1% liver metastases. Of the tested patients (n = 226), 73.9% had expressing PD-L1. 1L treatment comprised pembrolizumab + chemotherapy (CT) in 79.2%, pembrolizumab monotherapy in 12.1%, nivolumab + ipilimumab + CT in 6.7%, atezolizumab + bevacizumab + CT in 1.7%, and atezolizumab + CT in one patient (table).
Characteristics at 1L immunotherapy initiation
| Pembrolizumab | ||||
|---|---|---|---|---|
| Monotherapy | +CT | Nivolumab + ipilimumab + CT | Atezolizumab + CT ± bevacizumab | |
| N = 29 | N = 190 | N = 16 | N = 5 | |
| % of patients | ||||
| Age ≥70 years | 58.6 | 43.2 | 50.0 | 20.0 |
| Male | 65.5 | 76.8 | 81.3 | 60.0 |
| Ever smokers | 75.9 | 93.2 | 93.8 | 100.0 |
| Presence of comorbidity | 62.1 | 74.2 | 50.0 | 60.0 |
| ECOG Performance Status 0-1 | 82.8 | 94.7 | 100.0 | 100.0 |
| Stage IV disease | 75.9 | 94.7 | 100.0 | 100.0 |
| Adenocarcinoma | 62.1 | 72.1 | 31.3 | 100.0 |
| PD-L1 Tumor Proportion Score ≥50% | 96.6 | 21.9 | 14.3 | 20.0 |
Conclusions
These results yield novel RWE on the profile and IO treatment patterns of advanced/metastatic NSCLC patients in Greece. Such data help to better understand disease and therapy approaches so as to design informed health policy strategies.
Clinical trial identification
MK-3475-7755 (IO-HORIZON).
Editorial acknowledgement
Dr Visvikis for his clinical contribution to the study. Qualitis LTD for supporting the abstract write-up.
Legal entity responsible for the study
MSD Greece.
Funding
MSD Greece.
Disclosure
H. Linardou: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, Merck, Takeda, Bristol-Myers Squibb, Eli Lilly, Pfizer; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, Bristol-Myers Squibb, Pfizer, Amgen, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Bristol-Myers Squibb, Boehringer Ingelheim, Roche, AbbVie, Eli Lilly, Novartis, AstraZeneca, Amgen, PPD, Parexel ILR, Qualitis, Health Data Specialist; Non-Financial Interests, Personal, Principal Investigator: Hellenic Cooperative Oncology Group; Non-Financial Interests, Personal, Leadership Role, Elected President of the Scientific Committee: Hellenic Cooperative Oncology Group; Non-Financial Interests, Personal, Invited Speaker: Women 4 Oncology - Hellas, Fairlife Lung Cancer Care. A. Charpidou: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Roche. A. Koumarianou: Financial Interests, Personal, Invited Speaker: BMS, Genesis Pharma, Ipsen, Merck, MSD, Novartis, Pfizer, Roche. G. Mountzios: Financial Interests, Personal, Advisory Board: Roche, BMS, Takeda, Janssen; Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Pfizer, Novartis, Amgen. P.A. Kosmidis: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Registration in Congress: Pfizer; Financial Interests, Personal, Other, Registration to Congress: Sanofi; Financial Interests, Personal, Ownership Interest: Careacross Digital Health Company. C. Christodoulou: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Genesis Pharma, MSD, Novartis, Pfizer, Roche, Sanofi. D. Mavroudis: Financial Interests, Personal, Advisory Board: MSD. A.N. Christopoulou: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, BMS, Glaxo SmithKline, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sanofi. I. Korantzis: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Merck, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi. S. Baka: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Genesis Pharma, Eli Lilly, MSD, Novartis, Roche, Takeda. I. Athanasiadis: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Glaxo SmithKline, Ipsen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Servier. A. Koutras: Financial Interests, Personal, Advisory Board: Pierre Fabre, AstraZeneca, Gilead, Pfizer, Genesis; Financial Interests, Personal, Invited Speaker: Sanofi, Gilead; Financial Interests, Personal, Other, travel, accommodations: Rafarm, Eli Lilly, Ipsen, Gilead; Financial Interests, Institutional, Funding: Eli Lilly, Pfizer, Merck; Financial Interests, Institutional, Research Grant: AstraZeneca, Pierre Fabre, BMS, Demo, Faran, Amgen, Roche, Ipsen, Galenica, Win Medica. A. Kotsakis: Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, MSD, Roche. D. Ziogas: Financial Interests, Personal, Invited Speaker: MSD. A. Desiniotis: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ USA. I. Dimitriadis: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ USA. K. Syrigos: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Novartis, Pfizer, Roche, Takeda. All other authors have declared no conflicts of interest.
49P - Patient-reported outcomes (PROs) in patients with advanced non-small cell lung cancer (aNSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50% receiving cemiplimab (CEMI) monotherapy vs chemotherapy (CHEMO): EMPOWER-Lung 1 liver metastases subpopulation
- A. Baramidze (Tbilisi, Georgia)
- A. Baramidze (Tbilisi, Georgia)
- C. Gessner (Leipzig, Germany)
- M. Gogishvili (Tbilisi, Georgia)
- A. Sezer (Adana, Turkey)
- T. Makharadze (Batumi, Georgia)
- S. Kilickap (Istanbul, Turkey)
- M. Gumus (Istanbul, Turkey)
- X. He (Tarrytown, United States of America)
- G. Gullo (Tarrytown, United States of America)
- P. Rietschel (Tarrytown, United States of America)
- R. Quek (Tarrytown, United States of America)
Abstract
Background
In subgroup analyses of EMPOWER-Lung 1, a randomised 1:1 open-label phase III study, improvement in overall survival (OS) with CEMI (n = 48) vs CHEMO (n = 47) (median OS: not reached vs 7.4 months; HR: 0.38; 95% confidence interval [CI]: 0.19, 0.75) was observed in patients with aNSCLC with PD-L1 ≥ 50% and baseline liver metastases. In this post hoc analysis, we evaluated PROs.
Methods
PROs were assessed at baseline and Day 1 of each treatment cycle for the first 6 cycles, then on Day 1 of every third cycle using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Lung Cancer 13 (QLQ-LC13) questionnaires. Higher scores indicate better functioning and global health status (GHS)/quality of life (QoL) or worse symptom severity. Mixed-effects repeated-measures analyses were used to compare overall change from baseline scores between the treatment arms, controlling for baseline scores and other covariates.
Results
Statistically significant difference in overall change from baseline in physical functioning favoured CEMI vs CHEMO (6.24; 95% CI: 0.34, 12.14; P = 0.0384). CEMI also resulted in a statistically significant favourable difference vs CHEMO in overall change from baseline in the symptoms of nausea/vomiting (−3.80; 95% CI: −7.29, −0.31; P = 0.0334), alopecia (−15.75; 95% CI: −24.61, −6.88; P = 0.0007) and pain in arm or shoulder (−9.05; 95% CI:−16.67, −1.43; P = 0.0208). Compared with CHEMO, CEMI had numerically improved scores in GHS/QoL, all functioning scales, and 15 of 18 symptom scales. No analyses yielded statistically significant PRO results favouring CHEMO vs CEMI on any QLQ-C30 or QLQ-LC13 scales.
Conclusions
In patients with aNSCLC with PD-L1 ≥50% and baseline liver metastases, CEMI resulted in significant favourable overall change from baseline in physical functioning, nausea/vomiting, alopecia and pain in arm or shoulder symptoms vs CHEMO. PRO results further support the favourable benefit-risk profile of first-line CEMI vs CHEMO in patients with aNSCLC with PD-L1 ≥50% and baseline liver metastases.
Clinical trial identification
NCT03088540.
Editorial acknowledgement
Medical writing support was provided by John G Facciponte, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.
Legal entity responsible for the study
Regeneron Pharmaceuticals, Inc.
Funding
Regeneron Pharmaceuticals, Inc. and Sanofi.
Disclosure
A. Baramidze: Financial Interests, Personal, Other, Travel support: Regeneron Pharmaceuticals, Inc. C. Gessner: Financial Interests, Personal, Advisory Board: GlaxoSmithKline, Pfizer, AstraZeneca, Roche, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Berlin-Chemie, Chiesi, Boehringer Ingelheim, Sanofi. A. Sezer: Financial Interests, Institutional, Research Grant: Roche, Merck Sharp & Dohme, Merck Serono, AstraZeneca, Eli Lilly, Novartis, Johnson & Johnson, Regeneron Pharmaceuticals, Inc., Sanofi. M. Gumus: Financial Interests, Personal, Advisory Role, Honoraria: Roche, Merck Sharp & Dohme, Gen İlaç, Novartis. X. He: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. P. Rietschel: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. R. Quek: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.
50P - Patient-reported outcomes in non-small cell lung cancer patients receiving immunotherapy monotherapy: Analysis from enhanced, EHR-facilitated cancer symptom control (E2C2) pragmatic clinical trial
- B. Liu (Mankato, United States of America)
- B. Liu (Mankato, United States of America)
- V. Lam (Rochester, United States of America)
- D. Pachman (Rochester, United States of America)
- K. Ruddy (Rochester, United States of America)
- O. Burke (Rochester, United States of America)
- P. Lingamaneni (Rochester, United States of America)
- Y. Yu (Rochester, United States of America)
- G. Jiang (Rochester, United States of America)
- A. Cheville (Rochester, United States of America)
- K. Leventakos (Rochester, United States of America)
Abstract
Background
Immunotherapy has improved or maintained health-related quality of life (QOL) according to patient-reported outcomes (PROs) of non-small cell lung cancer (NSCLC) clinical trials. However, real-world evidence has been limited. Our study describes clinical outcomes and PROs in NSCLC while receiving immunotherapy monotherapy as first-line treatment using real-world data.
Methods
We retrospectively collected clinical data and PROs of adult patients with NSCLC who enrolled in Enhanced, EHR-facilitated Cancer Symptom Control (E2C2) pragmatic trial from 3/2019 to 11/2022. PROs were collected by survey in six domains including sleep disturbance, pain, anxiety, physical dysfunction, fatigue, and distress.
Results
Out of 31225 patients with cancer enrolled in E2C2 trial, one-hundred patients were identified to have received immunotherapy monotherapy as first-line treatment for NSCLC. Eighty-three patients had metastatic disease at initiation of immunotherapy; nine had stage III disease, and eight had recurrent disease. Ninety patients received pembrolizumab. Median length of therapy was 15 months. Sixty patients discontinued treatment by censor date; nineteen patients were on active treatment, and eighteen patients were on treatment holiday and active surveillance. Top reasons for discontinuation of therapy were progression (33.3%), immunotherapy-related adverse event (26.7%), and poor performance status (20%). A total of 999 PRO surveys were analyzed. The most frequent moderate to severe symptoms include physical dysfunction (76%), fatigue (75%), and sleeping disturbance (68%); pain (58%), anxiety (55%), and distress (49%) were less frequently reported. For a subgroup of patients (n = 50) whose baseline symptom measurement was available, there was a trend of moderate to severe symptoms decreasing over time.
Conclusions
Our study demonstrated that patients with NSCLC on immunotherapy monotherapy have significant symptom burden, particularly physical dysfunction, fatigue, and sleeping. Our study highlights the unmet supportive care needs of individuals living with NSCLC receiving immunotherapy.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
K. Leventakos: Non-Financial Interests, Personal, Invited Speaker: OncLive State of the Summit, MJH Life Sciences; Non-Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim Pharmaceuticals, Amgen; Non-Financial Interests, Institutional, Advisory Board: AstraZeneca, Targeted Oncology, Takeda, Jazz Pharmaceuticals, Mirati Therapeutics, Janssen, Regeneron; Non-Financial Interests, Institutional, Advisory Role, Research Support: AstraZeneca; Non-Financial Interests, Institutional, Advisory Role, Research support: Mirati Therapeutics – to institution. All other authors have declared no conflicts of interest.
51P - Real-word outcomes of immunotherapy in non-small cell lung cancer: A population-based cohort study in Sweden
- L. Wagenius (Stockholm, Sweden)
- L. Wagenius (Stockholm, Sweden)
- A. Vikström (Linköping, Sweden)
- A. Berglund (Uppsala, Sweden)
- S. Salomonsson (Sollentuna, Sweden)
- G. Bencina (Madrid, Spain)
- X. Hu (Rahway, United States of America)
- D. R. Chirovsky (Rahway, United States of America)
- H. Brunnström (Lund, Sweden)
Abstract
Background
In a previous study, we reported real-world PD-L1 testing rates, treatment patterns, and outcomes for patients with advanced non-small cell lung cancer (NSCLC) in the era of immuno-oncology in Sweden. In this follow-up study, with additional patients and 12 more months follow-up, the aim was further investigation with a focus on overall survival (OS) in the Swedish setting.
Methods
Data were extracted from the Swedish National Lung Cancer Registry for patients with unresectable stage IIIB-IV NSCLC and ECOG performance status (PS) 0–2 who initiated first-line (1L) PD-(L)1-based regimen from Apr 1, 2017 to Jun 30, 2021, with data cutoff Jun 30, 2022. Kaplan-Meier analysis was used to assess OS by histology and by PD-(L)1 combination therapy (combo) and monotherapy (mono) in patients with ECOG PS 0–1, where index date was defined as the start of 1L therapy.
Results
Of 1153 eligible patients, 669 (58%) received PD-(L)1 inhibitor combo and the remaining PD-(L)1 mono. The vast majority of patients treated with PD-(L)1 inhibitors initiated a pembrolizumab-based regimen: 294 (96%) and 62 (97%) initiated a pembrolizumab-based combo and 504 (85%) and 147 (76%) initiated pembrolizumab mono, in patients with nonsquamous and squamous histology, respectively. The table presents baseline demographics and OS data by histology and by type of PD-(L)1 regimen in patients with ECOG PS 0–1. For reference, in patients receiving 1L platinum-based combination regimen with ECOG PS 0–1 in this Registry, median OS was 10.2 and 11.7 months and the 12-month OS rate was 43.7% and 49.9% in patients with nonsquamous and squamous histology, respectively.
Baseline demographics and OS by histology in patients with ECOG PS 0–1
| Nonsquamous | Squamous | |||
|---|---|---|---|---|
| PD-(L)1 combo N = 305 | PD-(L)1 mono N = 590 | PD-(L)1 combo N = 64 | PD-(L1) mono N = 194 | |
| Female, % | 57.0 | 58.0 | 40.6 | 39.7 |
| Age, mean (SD), years | 68.0 (8.9) | 70.3 (8.5) | 68.3 (7.6) | 71.8 (8.2) |
| Event, N | 124 | 262 | 23 | 90 |
| Median OS (95% CI), months | 20.6 (15.9, 26.9) | 19.8 (17.6, 24.4) | 18.9 (14.1, NE) | 15.0 (11.6, 17.2) |
| OS rate (95% CI), % | ||||
| At 12 months | 64.9 (58.9, 71.5) | 64.2 (59.8, 68.9) | 71.3 (59.2, 86.0) | 57.8 (49.8, 67.1) |
| At 24 months | 45.4 (38.6, 53.3) | 45.9 (41.1, 51.2) | 44.6 (30.3, 65.6) | 30.6 (22.9, 41.0) |
| At 36 months | 33.1 (25.7, 42.6) | 33.1 (28.3, 38.8) | NE (NE, NE) | 19.4 (12.6, 30.0) |
Conclusions
Updated OS data from this nationally representative patient cohort with advanced NSCLC in Sweden are generally in alignment with OS results reported from PD-(L)1 inhibitor clinical trials, supporting the benefit of PD-(L)1 inhibitors as frontline therapy in clinical practice.
Legal entity responsible for the study
Merck & Co., Inc.
Funding
Merck & Co., Inc.
Disclosure
G. Wagenius: Financial Interests, Personal, Sponsor/Funding: MSD. A. Vikström: Financial Interests, Personal, Sponsor/Funding: MSD. A. Berglund: Financial Interests, Personal, Sponsor/Funding: MSD. S. Salomonsson: Financial Interests, Personal, Full or part-time Employment: MSD; Financial Interests, Personal, Stocks/Shares: MSD. G. Bencina: Financial Interests, Personal, Full or part-time Employment: MSD; Financial Interests, Personal, Stocks/Shares: MSD. X. Hu: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. D.R. Chirovsky: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. H. Brunnström: Financial Interests, Personal, Sponsor/Funding: MSD.
52P - Real-world versus clinical trial outcomes of pembrolizumab plus chemotherapy in patients with stage IV non-squamous non-small cell lung cancer
- M. Verschueren (Nieuwegein, Netherlands)
- M. Verschueren (Nieuwegein, Netherlands)
- V. Kruik (Nieuwegein, Netherlands)
- B. Peters (Nieuwegein, Netherlands)
- L. Bloem (Utrecht, Netherlands)
- A. Bijsmans (Rotterdam, Netherlands)
- T. Egberts (Utrecht, Netherlands)
- E. Van de Garde (Utrecht, Netherlands)
Abstract
Background
For many systemic treatments in oncology, a divergence between efficacy in clinical trials versus effectiveness in clinical practice has been observed. The present study investigated the real-world outcomes for pembrolizumab plus chemotherapy in patients with stage IV non-squamous non-small cell lung cancer (NSCLC) and compared these with the results of the KEYNOTE-189 trial.
Methods
This retrospective cohort study included all patients diagnosed with stage IV non-squamous NSCLC and treated with first-line pembrolizumab plus pemetrexed-platinum in 2019 and 2020 within a network of seven teaching hospitals (Santeon) in the Netherlands. The overall survival observed in the real-world was compared with the KEYNOTE-189 trial by calculating hazard ratios (HR) with 95% confidence intervals (95%CI) for the total population and PD-L1 subgroups.
Results
A total of 512 patients were included (median age 65 years, 49% males; 9% ECOG-PS 2, and 19% with brain metastasis). The median OS (mOS) was shorter in clinical practice than in the trial (13 vs 22 months) with a HR (95%CI) of 1.50 (1.26–1.79) (table). The divergence from the trial was most pronounced in patients with <1% PD-L1 expression (mOS 10 vs 17 months; HR 1.38, 95%CI 1.06–1.79). Early discontinuation of chemotherapy (<4 cycles platinum) was more frequent in the real-world than the trial (35 vs 18%).
The overall survival for stage IV non-squamous patients treated with pembrolizumab plus chemotherapy (real-world vs KEYNOTE-189)
| Real-world vs KEYNOTE-189 | ||
|---|---|---|
| mOS in months (n) | HR (95%CI) for OS | |
| Total population | 13 (512) vs 22 (410) | 1.50 (1.26–1.79) |
| PD-L1 subgroups | ||
| PD-L1 <1% | 10 (269) vs 17 (127) | 1.38 (1.06–1.78) |
| PD-L1 ≥1–49% | 20 (158) vs 22 (128) | 1.10 (0.80–1.51) |
| PD-L1 ≥50% | 26 (59) vs 28 (132) | 1.21 (0.76–1.89) |
| Unknown | 9 (26) vs NA (23) | NA |
Conclusions
This study showed considerably worse real-world mOS for pembrolizumab plus chemotherapy compared to the corresponding clinical trial. In patients with low PD-L1 expression, the benefit of pembrolizumab added to chemotherapy seems limited.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
53P - Real-world outcomes of first-line pembrolizumab (Pem) for metastatic non-small cell lung cancer (mNSCLC) with ≥50% expression of programmed cell death-ligand 1 (PD-L1): A multicentre retrospective study
- J. Perea (Valencia, Spain)
- J. Perea (Valencia, Spain)
- E. Gómez (Valencia, Spain)
- C. Escrivá (Valencia, Spain)
- A. V. Pellicer (Valencia, Spain)
- P. Llor Rodriguez (Valencia, Spain)
- J. Iranzo (Valencia, Spain)
- O. Juan Vidal (Valencia, Spain)
- J. García Sanchez (Valencia, Spain)
- G. Suay Montagud (Valencia, Spain)
- A. Ferrero Micó (Valencia, Spain)
- J. D. Linares Diaz (Valencia, Spain)
- N. Gómez Sepúlveda (Valencia, Spain)
- E. Soria Hernández (Valencia, Spain)
- J. M. Esteve Gallego (Valencia, Spain)
- C. Carrasco (Valencia, Spain)
- P. Capdevila Gaudens (Valencia, Spain)
Abstract
Background
Pem is the standard first-line treatment for mNSCLC patients based on the greater benefit showed in a well-designed phase III trial (Keynote-024). However, these data represent only a part of patients (pts) due to the strict selection criteria. Pts’ characteristics in clinical practice are more heterogeneous. The real-world data are useful to validate the trial results and find which patients are suitable for treatment.
Methods
Multicentre retrospective study of pts with mNSCLC and PD-L1 expression in tumour cells ≥50%, without actionable mutations, treated with first-line Pem at 2 hospitals in Valencia, Spain. Baseline factors, efficacy and adverse effects were collected. Statistical analysis was carried out with SPSS v25.0.
Results
From January 2017 to January 2021, 109 pts were treated. Median age 69. Men 81.7%. 19.8% had treated brain metastases, 47% had Performance Status (PS) <2. Median follow-up was 11 months (m). Median number of cycles administered was 8; 10 in pts with PS 0–1 and 5 in PS≥2. 43.5% of PS≥2 pts received less than 4 cycles (p = 0.007). Median Overall Survival (mOS) was 12 m (95% Confidence Interval, CI, 8.6–15.4), 16 m in PS 0–1 pts (12.7–19.2) and 10 m (12.6–14.3) in PS≥2 pts (p = 0.019). Median Progression Free Survival (mPFS) was 6 m (3.6–8.3), 10 m in PS 0–1 pts (4.6–15.4), and 4 m in PS≥2 (2.6–5.3) (p < 0.0001). Overall response rate was 43.7%, with 8.2% of complete responses. Disease control rate was 58.2%. Median time to onset of immune-related adverse events (irAEs) was 4 m. Toxicity of any degree was reported in 52.3%, grade (G) ≥3 in 15.6%. Hepatogastrointestinal (24.8%) and skin (20.2%) toxicities, the most common. mPFS in pts with irAEs was 11 m (7.2–14.8) and mOS 29 m (12–46), while those without irAEs had a mPFS of 2 m (0.8–3.2) (p < 0.0001) and mOS of 4 m (2–6) (p < 0.0001).
Conclusions
Real-world data confirm that Pem is an effective, tolerable option for mNSCLC pts with PD-L1 ≥ 50%. PS≥2 pts were not included in the Keynote-024 trial and this subgroup showed significantly shorter mPFS and mOS. The role of Pem in PS≥2 needs to be validated in a prospective phase III trial. Occurrence of irAEs is associated with an increase in mPFS and mOS.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
54P - Real-world efficacy of immunotherapy plus anti-angiogenesis versus immunotherapy monotherapy as second-line or later treatment in advanced non-small cell lung cancer
- Y. Zhang (Shanghai, China)
- Y. Zhang (Shanghai, China)
- H. Qiang (Shanghai, China)
- H. Zhong (Shanghai, China)
Abstract
Background
Previous clinical research has demonstrated that immunotherapy plus anti-angiogenesis have a synergistic effect and achieved promising clinical outcomes in treating advanced NSCLC patients as first-line therapy. However, there are limited data for immunotherapy plus anti-angiogenesis as second-line or salvage therapy. Herein, we conduct a retrospective study to evaluate the efficacy of immunotherapy in combination with anti-angiogenesis as second-line or later therapy for patients with advanced NSCLC in the real world.
Methods
We retrospectively enrolled eligible patients with advanced NSCLC who were treated with immunotherapy plus anti-angiogenesis (I+A group) or immunotherapy monotherapy (IM group) as second-line or later therapy at Shanghai Chest Hospital from January 1, 2018, to March 30, 2022. The clinical information was collected, and the treatment outcomes and survival data were assessed and compared between the two groups.
Results
A total of 211 patients were included in this study (83 patients in the I+A group and 128 patients in the IM group). The I+A group achieved a higher objective response rate (ORR) compared with the IM group (27.7% VS. 3.9%, P < 0.001). The median progression-free survival (PFS) was 6.77 months VS. 4.67 months (P < 0.001), and the median overall survival (OS) was 16.73 months VS. 12.63 months (P = 0.035), respectively. In the subgroup analysis, patients who received immunotherapy as second-line treatment were more likely to benefit from combination therapy (mPFS: 8.93months VS. 4.03 months, P < 0.001). Additionally, multivariate analysis showed that immunotherapy plus anti-angiogenesis had significantly prolonged the PFS and OS (P = 0.011 and P = 0.008).
Conclusions
Immunotherapy plus anti-angiogenesis achieved longer PFS and OS in patients with advanced NSCLC in the second-line or posterior treatment. Further prospective research should be conducted on larger populations.
Legal entity responsible for the study
The authors.
Funding
National Natural Science Foundation of China (No. 82072573, 82002426)
Disclosure
All authors have declared no conflicts of interest.
55P - Real-world monitoring of hybrid dosing of pembrolizumab in stage IV non-small cell lung cancer in the Netherlands
- E. Dronkers (Amsterdam, Netherlands)
- E. Dronkers (Amsterdam, Netherlands)
- E. Van Geffen (Amsterdam, Netherlands)
- C. Bekkers ('s-Hertogenbosch, Netherlands)
- A. Sobels (Den Haag, Netherlands)
- R. Van Drie-Pierik (Enschede, Netherlands)
- A. Eldering - Heldens (Alkmaar, Netherlands)
- J. Zwaveling (Leiden, Netherlands)
- J. Eijsink (Zwolle, Netherlands)
- H. J. Smit (Arnhem, Netherlands)
- D. Hilarius (Beverwijk, Netherlands)
Abstract
Background
In the Netherlands, pembrolizumab dosing guidelines have been altered from a fixed dose to hybrid dosing. Hybrid dosing reduces costs and helps to maintain a sustainable healthcare system, without compromising the safety and efficacy. Implementation of these new dosing guidelines can be challenging in daily clinical practice. The Dutch Institute for Clinical Auditing (DICA) medicine program was set up to help hospitals overcome these challenges by analyzing real-world drug use and discussing the different policies between hospitals. In this project we aimed to determine to what extent hybrid dosing is being used and aid to further implementation.
Methods
Clinical and claims data of stage IV non-small cell lung cancer patients from 2018–2022 were linked to analyze dosing strategies of pembrolizumab in the 26 Dutch hospitals that participated in the DICA medicine program. Standard dosing was defined as a fixed dose of 200 mg per three weeks or 400 mg per six weeks. Hybrid dosing was defined as 100 mg or 150 mg per three weeks, or 200 mg or 300 mg per six weeks depending on patients’ weight. Insights per hospital were discussed in a roundtable session with medical specialists and hospital pharmacists.
Results
Of the 26 hospitals involved, five prescribed pembrolizumab with hybrid dosing. Implementation of hybrid dosing increased between 2020 and 2022. One hospital reduced the dosage using a different dosing strategy. Within the hospitals that fully implemented hybrid dosing, a reduction of costs for pembrolizumab of 25% was observed. In the roundtable session hospital staff shared best practices. Technical limitation was among others mentioned as challenge to overcome by hospitals that did not implement hybrid dosing yet.
Conclusions
The DICA medicine program is a platform to use real-world data to improve quality of care. Clinical and claims data showed that hybrid dosing of pembrolizumab in NSCLC patients was only partially implemented in the Netherlands. Providing insights on implementation across hospitals and sharing best practices may support the implementation of guidelines. Because the DICA medicine program is connected with different clinical registrations, in the future real-world outcome of this new strategy can be assessed.
Legal entity responsible for the study
Dutch Institute for Clinical Auditing.
Funding
Zorgverzekeraars Nederland.
Disclosure
E. Dronkers: Financial Interests, Institutional, Funding: Zorgverzekeraars Nederland; Financial Interests, Personal, Full or part-time Employment: LOGEX. E. van Geffen: Financial Interests, Institutional, Funding: Zorgverzekeraars Nederland; Financial Interests, Personal, Full or part-time Employment: LOGEX. All other authors have declared no conflicts of interest.
56P - Pooled analysis of 4 studies evaluating weekly oral vinorelbine in patients with locally advanced or metastatic non-small cell lung cancer
- C. Chouaid (Créteil, France)
- C. Chouaid (Créteil, France)
- F. Grossi (Busto Arsizio, Italy)
- C. Ta Thanh Minh (Boulogne-Billancourt, France)
- R. Raymond (Boulogne-Billancourt, France)
- J. Bosch-Barrera (Girona, Spain)
Abstract
Background
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Vinorelbine (VNR) is an established treatment for advanced NSCLC, both as a single agent and in combination with platin chemotherapy. Four previous phase II, open-label clinical trials evaluated the efficacy and safety of oral VNR as monotherapy in NSCLC patients. Here, we aim to assess the efficacy and safety of oral VNR using pooled data.
Methods
This analysis included individual data of 4 phase II, open-label trials, focusing only on patients receiving oral VNR as monotherapy administered as standard weekly doses administration. Patients received VNR at the dose of 60 mg/m² weekly at cycle 1 (3weeks per cycle), followed by an increase to 80 mg/m² weekly for the subsequent cycles, until disease progression or toxicity. Main outcomes were overall response rate [ORR], disease control rate [DCR], progressive free survival [PFS] and overall survival [OS]), and tolerance.
Results
A total of 247 patients were included, and 244 were treated. The patient characteristics were: 75.7% of male patients, 81.4% of them had a stage IV, and 37.2% had squamous histology. The ECOG PS (Eastern Cooperative Oncology Group Performance Status) was 0, 1, ≥2, in respectively 40.9%, 45.7%, and 12.6% of patients. There were 108 patients (43.7%) with ≥ 3 organs involved. Overall, 243 patients received oral VNR for a total of 1176 cycles, representing a median number of 4 cycles per patient, and 73% of patients had dose escalation at cycle 2. ORR was 8.9% (95% confidence intervals [CI]: 5.7; 13.2), DCR was 57.5% (95% CI: 51.1; 63.7), median PFS and OS were 3.3 (95% CI: 2.8; 4.0) and 8.5 (95% CI: 7.6; 10.3) months, respectively.
Conclusions
This pooled analysis showed that weekly oral VNR dosing was a valid option in this population of patients with advanced or metastatic NSCLC, confirming the results from previous studies. Safety analysis will be presented at the meeting.
Clinical trial identification
Two of the studies used in this analysis do not have official designation CT (old studies). TEMPO LUNG, with European trial protocol number EudraCT 2014-003859-61. And the last trial used had European trial protocol number EudraCT 2012-003361-18.
Editorial acknowledgement
An editorial assistance in the writing of the abstract was provided by Keyrus Life Science and funded by Pierre Fabre.
Legal entity responsible for the study
Pierre Fabre Médicament.
Funding
Pierre Fabre Médicament.
Disclosure
C. Chouaid: Financial Interests, Personal and Institutional, Training: AstraZeneca, Boehringer Ingelheim, Clovis, GlaxoSmithKline, Hoffmann La Roche, GSK, Eli Lilly, Pfizer, BMS, MSD, Novartis, Accord Healthcare, Sandoz, Janssen, Takeda, Sanofi, Pierre Fabre and Amgen; Financial Interests, Personal and Institutional, Expert Testimony: AstraZeneca, Boehringer Ingelheim, Clovis, GlaxoSmithKline, Hoffmann La Roche, GSK, Eli Lilly, Pfizer, BMS, MSD, Novartis, Accord Healthcare, Sandoz, Janssen, Takeda, Sanofi, Pierre Fabre and Amgen; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Clovis, GlaxoSmithKline, Hoffmann La Roche, GSK, Eli Lilly, Pfizer, BMS, MSD, Novartis, Accord Healthcare, Sandoz, Janssen, Takeda, Sanofi, Pierre Fabre and Amgen; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Boehringer Ingelheim, Clovis, GlaxoSmithKline, Hoffmann La Roche, GSK, Eli Lilly, Pfizer, BMS, MSD, Novartis, Accord Healthcare, Sandoz, Janssen, Takeda, Sanofi, Pierre Fabre and Amgen; Financial Interests, Personal and Institutional, Other, Clinical research: AstraZeneca, Boehringer Ingelheim, Clovis, GlaxoSmithKline, Hoffmann La Roche, GSK, Eli Lilly, Pfizer, BMS, MSD, Novartis, Accord Healthcare, Sandoz, Janssen, Takeda, Sanofi, Pierre Fabre and Amgen. F. Grossi: Financial Interests, Personal and Institutional, Advisory Board: Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, Pierre Fabre, BMS, MSD, Novartis, Merck, Otsuka, Novartis, Takeda, Bayer. C. Ta Thanh Minh: Financial Interests, Personal, Full or part-time Employment: Pierre Fabre. R. Raymond: Financial Interests, Personal, Full or part-time Employment: Pierre Fabre. J. Bosch-Barrera: Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Outside the submitted work: Pfizer, MSD, BMS, AstraZeneca Boehringer Ingelheim, Vifor, Sanofi.
57P - A study of gemcitabine-cisplatin vs paclitaxel-carboplatin chemotherapy in patients with advanced squamous cell carcinoma of the lung
- T. Rajan (Chennai, India)
- T. Rajan (Chennai, India)
Abstract
Background
Squamous cell carcinoma accounts for about 20% of all lung cancers. Gemcitabine-cisplatin and paclitaxel-carboplatin are the two commonly used combination chemotherapeutic regimens in advanced squamous cell carcinoma of lung where we have no access to the novel therapeutics such as immunotherapy, with proven benefit in terms of response rate, survival, and also they are tolerated by the majority of patients.
Methods
This prospective observational study was conducted in patients diagnosed with stage IV squamous cell carcinoma of lung in the department of Radiation Oncology of Government Medical College, Trivandrum, from April 2018-September 2019. Due to the non-availability of PDL1 testing and novel immunotherapeutics, these patients were started on palliative chemotherapy either with gemcitabine-cisplatin and paclitaxel-carboplatin. After 4 cycles of chemotherapy CT thorax taken was assessed for the tumour response to treatment. The primary outcome was overall response rate (ORR), which was defined as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria, after completion 4 cycles of chemotherapy. Secondary outcome includes the incidence and grade of toxicity of the above two regimens.
Results
194 patients were taken up for the study. Overall response was 26% in paclitaxel-carboplatin arm and 27% in gemicitabine-cisplatin arm (p value- 0.76) and it was not statistically significant among the 2 regimens. Grade 3 and 4 anemia and neutropenia was seen more with paclitaxel-carboplatin compared to gemcitabine cisplatin (4% vs 0% and 4% vs 0%) (p value < 0.01). Grade 3 and 4 thrombocytopenia was also seen more among paclitaxel-carboplatin than in gemicitabine-cisplatin and it was statistically significant (4% vs 0%; p value < 0.01). Grade 3 and 4 nausea & vomiting was seen more in the gemicitabine-cisplatin arm but it was not statistically significant (8% vs 4%); (pvalue 0.07). There was no grade 3 or 4 renal toxicity, electrolyte abnormality or hearing loss in our study population.
Conclusions
We concluded that the overall response rate was similar in both treatment groups. Therefore both can be viewed as an acceptable option when we have no access to novel immunotherapeutics.
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
58P - Treatment combinations in non-driver mutated mNSCLC: A systematic review and Bayesian network meta-analysis
- P. Umesh (New Delhi, India)
- P. Umesh (New Delhi, India)
- K. S. Chufal (New Delhi, India)
- I. Ahmad (New Delhi, India)
- R. Bajpai (Staffordshire, United Kingdom)
- A. A. Miller (Wollongong, Australia)
- R. Chowdhary (New Delhi, India)
- M. I. Sharief (New Delhi, India)
- A. Dekker (Maastricht, Netherlands)
- L. Wee (Maastricht, Netherlands)
- A. M. Ansari (New Delhi, India)
- M. Gairola (New Delhi, India)
Abstract
Background
To compare the relative survival benefits & toxicities among treatments for non-driver mutated metastatic NSCLC (mNSCLC).
Methods
RCTs since inception, to June 1st 2021, were systematically searched from databases, trial registries & annual meeting abstracts. All trials comparing survival & toxicity between at least two of the following treatments were included: chemotherapy (CT) (single/multi-agent); PD1, PDL1 or CTLA4 immune checkpoint inhibitors (ICI) (single/multi-agent) (with/without CT), &; radiotherapy followed by either chemotherapy (RT+CT) or immune checkpoint inhibitors. The primary outcomes were risk of death at 1 year, risk of progression at 6 months & 1 year, & overall grade 3 or higher (G3+) toxicities. A Bayesian network meta-analysis using a random-effects model & empirical Markov Chain Monte Carlo simulation of multiple interventions was used. Results were expressed as risk ratios (RR)[95% Credible Interval (CrI)] & ranked using SUCRA scores. All CT regimens were merged into a single category & ICIs were divided into two categories (PD1 or PDL1; CTLA-4). Local & global consistency and sensitivity analyses were performed on the network (after splitting treatments). All treatments satisfied the transitivity assumption. Risk-of-bias (RoB) & confidence were assessed with Cochrane RoB & CiNeMA tools.
Results
30 RCTs (n = 14904; 36 possible comparisons; 12 direct comparisons) comparing 9 treatments were included. The combination of RT+PD1/PDL1 was ranked highest & demonstrated the lowest risk of death [RR = 0.47 (0.30–0.72)][SUCRA = 95%], progression [6 m RR = 0.39 (0.23–0.63)[SUCRA = 96%]; 1 yr RR = 0.74 (0.59–0.95)][SUCRA = 87%], & G3+ toxicities [RR = 0.74 (0.57–0.96)][SUCRA = 81%]. Results are shown below [RR (95% CrI)]. All sensitivity analyses favored RT+PD1/PDL1 over other treatments.
Results
| Death-1yr | Progression-6m | Progression-1yr | G3+Toxicity | |
|---|---|---|---|---|
| CT + RT | 0.56 (0.3–0.92) | 0.47 (0.26–0.77) | 0.77 (0.55–1) | 0.77 (0.55–0.99) |
| CTLA4 | 0.93 (0.69–1.21) | 1.07 (0.84–1.35) | 0.97 (0.88–1.05) | 0.85 (0.58–1.16) |
| CTLA4 + CT | 0.85 (0.60–1.2) | 0.89 (0.65–1.23) | 1 (0.93–1.08) | 0.82 (0.68–0.96) |
| PD1/PDL1 | 0.84 (0.79–0.9) | 0.91 (0.85–0.97) | 0.9 (0.89–0.92) | 0.9 (0.87–0.93) |
| PD1/PDL1 + CT | 0.84 (0.77–0.92) | 0.7 (0.63–0.78) | 0.83 (0.8–0.86) | 0.85 (0.81–0.9) |
| PD1/PDL1 + CTLA4 | 0.86 (0.75–0.99) | 0.9 (0.78–1.04) | 0.86 (0.82–0.9) | 0.87 (0.8–0.94) |
| PD1/PDL1 + CTLA4 + CT | 0.7 (0.54–0.9) | 0.7 (0.57, 0.97) | 0.8 (0.77–0.91) | 0.8 (0.73–0.96) |
| PD1/PDL1 + RT | 0.47 (0.3–0.72) | 0.39 (0.23–0.63) | 0.74 (0.59–0.95) | 0.74 (0.57–0.96) |
Conclusions
The results suggest that combining RT with PD1/PDL1 inhibitors could improve outcomes over other treatments in non-driver mutated metastatic NSCLC.
Legal entity responsible for the study
K. S. Chufal.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
59P - Assessment of QoL results and correlation with survival outcomes in phase III clinical trials in metastatic NSCLC
- A. Servetto (Napoli, Italy)
- A. Servetto (Napoli, Italy)
- F. Salomone (Napoli, Italy)
- F. Napolitano (Napoli, Italy)
- A. Santaniello (Napoli, Italy)
- L. Formisano (Napoli, Italy)
- R. Bianco (Napoli, Italy)
Abstract
Background
In addition to improvements of survival outcomes, new oncology treatments should lead to amelioration of patients’ quality of life (QoL). In patients with non-small lung cancer (NSCLC), a potential correlation between QoL results with progression-free survival (PFS) and overall survival (OS) outcomes is unknown.
Methods
We examined whether QoL results correlated with PFS and OS outcomes in phase III randomized controlled trials (RCTs) investigating new systemic treatments in metastatic non-small cell lung cancer (NSCLC), published between 2012 and 2021. Our systematic review identified 81 RCTs for further analysis.
Results
Compared to control arms, experimental treatments led to superior QoL in 30 (37.0%) RCTs and inferior QoL in 3 (3.7%) RCTs. In the remaining 48 (59.3%) RCTs, a statistically significant difference between experimental and control arms was not found. QoL results did not positively correlate with OS outcomes (X2 = 0.81, p = 0.368). Instead, we found a statistically significant correlation between QoL and PFS improvements (X2 = 3.93, p = 0.0473). More in detail, this correlation was not significant in trials testing immunotherapy or chemotherapy. On the contrary, in RCTs testing target therapies QoL results positively correlated with PFS outcomes (p = 0.0196). This correlation was stronger in the 32 trials testing EGFR or ALK inhibitors (p = 0.0077). Furthermore, we found that experimental treatments led to superior QoL in 27/57 (47.4%) trials with positive results and in 3/24 (12.5%) RCTs with negative results (p = 0.0028). Next, we analyzed how QoL data were described in publications of RCTs in which QoL outcomes were not improved (n = 51). We found that a favorable description of QoL results was associated with sponsorship by industries (p = 0.0232).
Conclusions
Our study reveals a positive correlation of QoL results with PFS outcomes, but not with OS, in RCTs testing novel treatments in advanced NSCLC, particularly for target therapies. Moreover, inappropriate description of QoL data was more frequent in RCTs funded by pharma companies.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Servetto: Non-Financial Interests, Personal, Other, Travel Support: Bristol-Myers Squibb, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant, Research funding: Associazione Italiana per la Ricerca sul Cancro. L. Formisano: Financial Interests, Personal and Institutional, Research Grant: Associazione Italiana per la Ricerca sul Cancro. R. Bianco: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb, MSD, AstraZeneca, Eli Lilly, Roche, Novartis; Financial Interests, Personal and Institutional, Research Grant, Funding for research: Associazione Italiana per la Ricerca sul Cancro. All other authors have declared no conflicts of interest.
60P - Comparison of metastasis patterns and prognosis of advanced old NSCLC patients by age groups: A SEER database analysis
- Y. Lingqi (Tianjin, China)
- Y. Lingqi (Tianjin, China)
- S. Xu (Tianjin, China)
Abstract
Background
We aimed to investigate the different metastatic patterns and corresponding survival outcomes between early age of elderly (aged between 65 to 80 years) and late age of elderly (aged more than 80 years) stage IV NSCLC patients.
Methods
Stage IV old NSCLC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016 were divided into an early age and late age of elderly group. To reduce the bias of retrospective studies, propensity score matching (PSM) analysis was performed. Baseline characteristics of patients were analyzed by the t test and chi- square test. Overall survival (OS) and lung cancer specific survival (LCSS) were evaluated by Kaplan-Meier curves and Cox proportional hazards models. Univariate and multivariate Cox regression models were used to analyze survival outcomes and other prognostic factors. Finally, a nomogram was constructed and validated to predict patient survival time.
Results
From the SEER database, a total of 47 438 old patients with stage IV NSCLC from 2010 to 2016 were enrolled in this cohort study. X-tile analysis identified the optimal cutoff age for LCSS as 80 years old. In this study, 35 385 patients aged 65–80 years and 12 052 patients aged over 85 years were included. After 1:1 PSM analysis, 10 931 patients aged 65–80 years and 10 931 patients aged over 85 years were ultimately included. Adenocarcinoma was the dominant histological subtype across each age group, particularly in the younger group. With aging, the proportion of patients undergoing treatment, including surgery, radiation, and chemotherapy, progressively declined. Compared with younger NSCLC patients, lung metastases were significantly more frequent in the elderly group, and lung metastases and distant lymph nodes metastases were independent prognostic factors of LCSS [lung metastases: hazard ratio (HR): 0.890; distant lymph nodes metastases: hazard ratio (HR): 0.844, all P values were <0.001]. In each age subgroup, patients with multi-organ metastasis had the worst LCSS.
Conclusions
Various clinicopathological features and prognostic values are associated with different metastatic sites. Understanding these differences may enable targeted pre-treatment assessment of advanced old NSCLC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding
Disclosure
All authors have declared no conflicts of interests.
61P - Early palliative care in patients with non-small cell lung cancer: A 36-weeks randomised controlled trial in China
- M. Chen (Chongqing, China)
- M. Chen (Chongqing, China)
- H. Yu (Chongqing, China)
Abstract
Background
Effective interventions to improve prognosis in non-small-cell lung cancer (NSCLC) are urgently needed. We assessed the effect of the early integration of interdisciplinary palliative care for patients with NSCLC on the nutritional status, quality of life (QoL), psychological state and cancer pain.
Methods
In this randomised controlled trial, 280 newly diagnosed NSCLC patients were enrolled and randomly assigned (1:1) to the combined early palliative care (CEPC) group integrated with standard oncologic care or standard oncological care (SC) group. QoL and psychological state were assessed at baseline and at 36 weeks by Functional Assessment of Cancer Therapy-Lung (FACT-L) scale, the Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire-9 (PHQ-9), respectively. Cancer nutritional and pain status were assessed with the use of the Patient-Generated Subjective Global Assessment (PG-SGA) and Numerical Rating Scale (NRS), respectively. The primary outcome was the change in the quality of life, psychological state and nutritional status at 36 weeks. Analysis was by intention to treat.
Results
280 patients were enrolled: 140 in CEPC group (88 completed) and 140 in the SC group (62 completed). Patients in CEPC group had a better nutritional status [severe malnutrition: 10.71% (15/140); mild or moderate malnutrition: 60.71% (85/140); no malnutrition: 26.4% (37/140)] than SC group [severe malnutrition: 35.71% (50/140); mild or moderate malnutrition: 55.0% (77/140); no malnutrition: 7.86% (11/140)] (P = 0.001). Furthermore, CEPC group had a better QoL than SC group (P < 0.05). In addition, fewer patients in the CEPC group than in the SC group had depressive (P = 0.005) symptoms. There was no significant difference in NRS score between CEPC group and SC group.
Conclusions
Among patients with non-small-cell lung cancer, early palliative care led to significant improvements in nutritional status, quality of life and psychological state.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
62P - Predictive value of combined positive score (CPS) and tumor proportion score (TPS) for immunotherapy response in advanced non-small cell lung cancer (NSCLC)
- E. B. Ulas (Amsterdam, Netherlands)
- E. B. Ulas (Amsterdam, Netherlands)
- S. Hashemi (Amsterdam, Netherlands)
- I. Houda (Amsterdam, Netherlands)
- A. Kaynak (Amsterdam, Netherlands)
- J. Veltman (Amsterdam, Netherlands)
- M. Fransen (Amsterdam, Netherlands)
- T. Radonic (Amsterdam, Netherlands)
- I. Bahce (Amsterdam, Netherlands)
Abstract
Background
In advanced stage non-small cell lung cancer (NSCLC), tumor proportion score (TPS) is typically used to predict the efficacy of immune checkpoint inhibitors (ICI). However, in other cancer types, the combined positive score (CPS), which covers PD-L1 expression on both tumor and surrounding immune cells, is used. We investigated the predictive value of CPS in comparison to TPS in advanced NSCLC.
Methods
A monocenter retrospective study was performed in advanced NSCLC patients treated with ICI monotherapy between 2015 and 2021. H&E and PD-L1 were stained on baseline tumor biopsies to score PD-L1 by both TPS and CPS. Positivity for TPS and CPS was defined as a score of 1% or above. Progression-free survival (PFS) and overall survival (OS) were assessed for TPS and CPS scores.
Results
Amongst the 187 included patients, PD-L1 positivity was found in 112 patients (59.9%) by TPS and 135 patients (72.2%) by CPS. In terms of PFS, no significant differences were observed between TPS− and TPS+ or CPS− and CPS+ patients (HR 0.86, p = 0.37 and HR 0.72, p = 0.065, respectively). There was no significant difference in OS between TPS− and TPS+ patients (HR 0.81, 95%CI 0.59–1.12, p = 0.20). However, CPS+ patients did show a longer OS than CPS− patients (HR 0.62, 95%CI 0.44–0.87, p = 0.006). OS was superior in both TPS−/CPS+ and TPS+/CPS+ as compared to TPS−/CPS− cases (HR 0.52, p = 0.018 and HR 0.64, p = 0.015, respectively). Cases that were TPS−/CPS+ had a comparable OS to TPS+/CPS+ cases (11.3 vs 9.7 months, p = 0.016).
Conclusions
To our knowledge, this is the largest real-world population study comparing TPS and CPS in NSCLC. We showed that CPS differentiated OS better than TPS in advanced NSCLC patients with ICI monotherapy. Remarkably, this was driven by the performance of the TPS−/CPS+ subgroup, indicating that CPS may be a better predictive biomarker for ICI efficacy. These findings support the notion that ICI also have an anti-cancer efficacy through inhibiting the immune suppressive immune cells in the tumor microenvironment.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Hashemi: Other, Institutional, Other, Research contracts to the institution, outside of the current study: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Janssen, GSK, MSD, Novartis, Roche, Takeda. All other authors have declared no conflicts of interest.
63P - Inflammatory indexes and treatment response as correlates of pembrolizumab effectiveness in patients with PD-L1≥50%: Data from the real-life practice
- M. Knetki-Wroblewska (Warsaw, Poland)
- M. Knetki-Wroblewska (Warsaw, Poland)
- S. TABOR (Warsaw, Poland)
- A. Pluzanski (Warsaw, Poland)
- K. Winiarczyk (Warsaw, Poland)
- P. Sobczuk (Warsaw, Poland)
- Z. Lewandowska (Warsaw, Poland)
- A. Piórek (Warsaw, Poland)
- K. Zajda (Warsaw, Poland)
- A. Janowicz-Zebrowska (Warsaw, Poland)
- M. Zaborowska-Szmit (Warsaw, Poland)
- P. Badurak (Warsaw, Poland)
- M. Borucka (Warsaw, Poland)
- D. M. Kowalski (Warsaw, Poland)
- M. Krzakowski (Warsaw, Poland)
Abstract
Background
Pembrolizumab is the standard first-line option for patients with metastatic non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression of ≥50%. Clinicopathological correlates of effectiveness in real-life populations remain unclear.
Methods
This study is a single-center retrospective analysis of patients (pts) with stage IV NSCLC treated with pembrolizumab in routine practice. Inclusion criteria included good performance status (ECOG 0–1), no active brain metastases, and no EGFR or ALK alterations. The median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The log-rank test and Cox regression model were used for uni- multivariate analysis.
Results
A group of 240 pts was included, of whom 20% were >75 years old, 10% had brain and 14% liver metastases. The ORR was 34%, 23% of pts had progressive disease, while 17% of pts has before the first radiological assessment. Median PFS and OS were 8.4 months (95% CI 4.9–11.8; 153 events) and 13.8 months (95% CI 10.47–17.12; 141 events), respectively. Adverse events (AEs) were reported in 28% of pts, including irAE in 18.8%. AEs led to treatment discontinuation in 10.3% of pts, and resulted in death in 2%. In the univariate analysis, tumor burden <110 mm (p < 0.04), neutrophils/lymphocytes ratio (NLR) <2.64 (p < 0.009), platelet/lymphocyte ratio (PLR) <256 (p < 0.024), monocyte/lymphocyte ratio (MLR) <37 (0.030), and Systemic Inflammatory Index <1309 (p < 0.003) and the Lung Immune Prognostic Index (LIPI) of 0 (p < 0.038) had a favorable impact on OS. Other pretreatment evaluated factors- age >75 years included- were not relevant. Early PD was a negative prognostic factor, with substantially shorter OS (p < 0.001). In multivariate analysis, the trend for a negative impact on OS of larger tumor burden was observed (p < 0.090, HR 1.35 95% CI 0.95–1.9).
Conclusions
The results of treatment with pembrolizumab in real-life are not as favorable as those obtained in the clinical trial setting. Taking into account additional factors - such as tumor burden and inflammatory indices - may be helpful in identifying the optimal patient population.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Knetki-Wroblewska: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Roche, MSD, Takeda, Amgen, AstraZeneca, Boehringer Ingelheim, Ipsen; Financial Interests, Personal, Advisory Board: Takeda, Boehringer Ingelheim, Bristol Myers Squibb. S. Tabor: Financial Interests, Personal, Invited Speaker: MSD. A. Płużański: Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca, Roche, Takeda, Pfizer; Financial Interests, Personal, Advisory Board: BMS, Takeda, MSD. K. Winiarczyk: Financial Interests, Personal, Invited Speaker: MSD, BMS, Pfizer. P. Sobczuk: Financial Interests, Personal, Other, Travel grant: Novartis; Financial Interests, Personal, Other, Travel Grant: MSD, Pierre Fabre, BMS; Financial Interests, Personal, Invited Speaker: Swixx BioPharma, BMS, Gilead; Financial Interests, Personal, Stocks/Shares: CelonPharma; Non-Financial Interests, Personal, Leadership Role, Board Member, Chair of Young Oncologists Section: Polish Society of Clinical Oncology. A. Piórek: Financial Interests, Personal, Invited Speaker: MSD, BMS. K. Zajda: Financial Interests, Personal, Invited Speaker: MSD, BMS, Roche. M. Zaborowska-Szmit: Financial Interests, Personal, Invited Speaker: MSD, BMS, Pfizer, Roche. P. Badurak: Financial Interests, Personal, Invited Speaker: BMS, MSD, Roche. D.M. Kowalski: Financial Interests, Personal, Invited Speaker: MSD, BMS, Roche, Pfizer, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: BMS, MSD, Takeda. M. Krzakowski: Financial Interests, Personal, Advisory Board: BMS, Roche, Amgen, MSD, AstraZeneca; Financial Interests, Personal, Other, Travel grant: BMS, Roche, AstraZeneca. All other authors have declared no conflicts of interest.
64P - Pretreatment predictive score for metastatic non-small cell lung cancer patients treated with immunotherapy
- A. Musaelyan (Saint-Petersburg, Russian Federation)
- A. Musaelyan (Saint-Petersburg, Russian Federation)
- F. Moiseyenko (Saint-Petersburg, Russian Federation)
- T. Emileva (Saint-Petersburg, Russian Federation)
- A. P. Oganesyan (Saint-Petersburg, Russian Federation)
- M. Urtenova (Saint-Petersburg, Russian Federation)
- S. Odintsova (Saint-Petersburg, Russian Federation)
- I. Chistyakov (Saint-Petersburg, Russian Federation)
- A. Akopov (Saint-Petersburg, Russian Federation)
- S. Orlov (Saint-Petersburg, Russian Federation)
Abstract
Background
Immune checkpoint inhibitors (ICIs) demonstrated efficacy in NSCLC patients, but only minority of them archive a clinical benefit from the therapy. The aim of the study was to investigate predictive value of the new score based on pretreatment markers in NSCLC patients treated with ICIs.
Methods
The study included 181 patients with EGFR/ALK-negative metastatic NSCLC receiving anti-PD-1/PD-L1 monotherapy in second and subsequent lines. The clinical, morphological and laboratory parameters were obtained before the start of treatment in all patients included in the study. The endpoints were overall survival (OS) and progression-free survival (PFS).
Results
Overall median of OS and PFS was 13,7 and 4,9 months, respectively. Multivariate analysis for OS determined baseline neutrophil-to-lymphocyte ratio (NLR) >4.3 (HR 4.89, 95% CI: 3.16–7.62, p < 0.0001), non-smokers (HR 1.80, 95% CI: 1.21–2.68, p = 0.004) and ECOG ≥2 (HR 2.02, 95% CI: 1.06–3.91, p = 0.035) as negative prognostic factors. The multivariate analysis for PFS also indicated these markers as independent predictors of resistance to ICIs. The three parameters were included in the NSE score (NLR- 2 points, Smoking status- 1, ECOG- 1 point). According to the score patients were classified into 3 groups: good (0 point), intermediate (1–2 points) and poor prognosis (≥3 points). The median of OS for good, intermediate and poor outcomes were 33.7, 12.2 and 7.2 months, respectively (p < 0.0001). Also, the NSE score could predict PFS in NSCLC patients: the median was 17.1, 4.3 and 3.2 months for good, intermediate and poor prognostic groups (p < 0.0001).
Conclusions
The NSE score including pretreatment clinical and blood markers can help to predict survival in NSCLC patients receiving ICIs in second and subsequent lines.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
65P - Correlation of overall survival and surrogate endpoints in advanced non-small cell lung cancer treated with immune checkpoint inhibitors: A trial-level analysis
- F. Salomone (Napoli, Italy)
- F. Salomone (Napoli, Italy)
- F. Napolitano (Napoli, Italy)
- A. Caltavituro (Napoli, Italy)
- R. Buonaiuto (Napoli, Italy)
- G. Pecoraro (Napoli, Italy)
- M. Isernia (Napoli, Italy)
- A. Santaniello (Napoli, Italy)
- L. Formisano (Napoli, Italy)
- R. Bianco (Napoli, Italy)
- A. Servetto (Napoli, Italy)
Abstract
Background
Immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, have radically changed treatment of patients with non-small cell lung cancer (NSCLC). We investigated whether progression-free survival (PFS) and objective response rate (ORR) correlate with overall survival (OS) in phase III randomized controlled trials (RCTs) testing ICIs in advanced NSCLC.
Methods
We systematically reviewed literature to select articles of RCTs investigating ICIs in advanced NSCLC, published by December 2022. For each RCT, we collected data about ORR, hazard ratio of OS (HROS) and PFS (HRPFS). When not reported, odds ratio for ORR (ORORR) was manually calculated. Spearman's rank correlation coefficient (ρ) was used to evaluate the relationship between: i) HROS and HRPFS; ii) HROS and ORORR. Absolute value of ρ indicated the power of correlation between the two variables (0.9–1.0 very strong, 0.7-<0.9 strong, 0.5-<0.7 moderate, 0.3-<0.5 weak, 0-<0.3 negligible).
Results
We identified 25 RCTs with 2 distinct arms and 5 trials with >2 experimental arms. Overall, 36 experimental arms of ICIs ± chemotherapy (ChT), versus standard ChT, were considered for further investigation. Analysis of trials results revealed a weak positive correlation between HROS-HRPFS (n = 35, ρ = 0.4562, p = .0059) and a moderate negative correlation between HROS-ORORR (n = 36, ρ = -0.6029, p < .001). HROS-HRPFS had a moderate positive relationship in studies testing ICIs in first-line setting (n = 27, ρ = 0.5681, p = .002), as well as in RCTs testing ICIs alone (n = 18, ρ = 0.5498, p = .018). Next, HROS-ORORR showed only a weak negative relationship in RCTs of ICIs alone (n = 18, ρ = -0.4694 p = .049). Finally, we found that PFS and ORR strongly correlated to OS in trials testing ICIs combined with ChT (n = 17, HROS-HRPFS ρ = 0.7606, p < .001; n = 18, HROS-ORORRρ = -0.8388, p < .001).
Conclusions
Across trials investigating ICIs in advanced NSCLC, PFS and ORR demonstrated plausible relationship with OS, particularly in RCTs testing combination of ICIs+ChT. However, our results show that caution should be taken when novel treatments are approved based on surrogate outcomes.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Formisano: Financial Interests, Personal and Institutional, Research Grant: AIRC. R. Bianco: Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca, Eli Lilly, Roche, Novartis; Financial Interests, Personal and Institutional, Research Grant: AIRC. A. Servetto: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AIRC. All other authors have declared no conflicts of interest.
66P - Outcome predictors for pembrolizumab alone or with chemotherapy in advanced non-small cell lung cancer (NSCLC)
- L. Zullo (Genova, Italy)
- L. Zullo (Genova, Italy)
- E. Cella (Genova, Italy)
- F. Paoloni (Ancona, Italy)
- M. Gualtieri (Ancona, Italy)
- G. Barletta (Genova, Italy)
- D. Favero (Genova, Italy)
- F. Parisi (Genova, Italy)
- C. Dellepiane (Genova, Italy)
- G. Rossi (Genova, Italy)
- E. Bennicelli (Genova, Italy)
- L. Zinoli (Genova, Italy)
- L. Cantini (Ancona, Italy)
- F. Pecci (Ancona, Italy)
- L. Del Mastro (Genova, Italy)
- R. Berardi (Ancona, Italy)
- C. Genova (Genova, Italy)
Abstract
Background
Apart from PD-L1 expression, no predictors for choosing between Pembrolizumab (Pembro) or Pembrolizumab-chemotherapy (Pembro-CT) as frontline treatment for advanced NSCLC are validated. Here we explore the potential role of different clinical, radiological, biological factors.
Methods
We retrospectively collected data from 112 and 84 patients, selected for Pembro or Pembro-CT solely based on PD-L1 as per Italian prescribing limitation (combination treatment reserved to PD-L1<50%), at two health facilities, and evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR).
Results
Median follow-up was 12.5 and 10.4 months for Pembro and Pembro-CT groups, respectively. The multiple analyzed sub-groups and their OS data are reported in
| Pembro | Pembro-CT | P | |
|---|---|---|---|
| OS (m) | 14.4 | 13.4 | 0.6 |
| Male | 16.5 | 12.6 | 0.09 |
| Female | 20.3 | NR | 0.32 |
| Non squamous | 20.3 | 12.6 | 0.41 |
| Squamous | 15.5 | 13.4 | 0.6 |
| Never smokers | 23.3 | 12.6 | 0.44 |
| Age>70 | 16.0 | 12.5 | 0.35 |
| PS ECOG≥2 | 2.5 | 1.5 | 0.34 |
| KRAS mutant | 9.7 | 16.0 | 0.33 |
| Tumor burden>62 mm | 10.9 | 10.9 | 0.91 |
| N# lesions >3 | 13.9 | 10.9 | 0.32 |
| Brain metastases | 8.7 | 9.0 | 0.6 |
| LIPI intermediate | 20.3 | 16.0 | 0.8 |
| Poor | 5.9 | 5.5 | 0.64 |
| Corticosteroids>10 mg/day | 2.7 | 8.6 | 0.38 |
| Proton pump inhibitors | 9.2 | 10.4 | 0.93 |
Conclusions
While no significant differences were found in OS, some patients, notably those harboring KRAS alterations, may benefit from the addition of chemotherapy. The enrichment of Pembro-CT group, together with molecular data revealing potential co-mutations, would provide more robust findings.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. Barletta: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Pierre Fabre, GlaxoSmithKline, Bristol-Myers Squibb. C. Dellepiane: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche. G. Rossi: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen, Roche. E. Bennicelli: Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb. L. Cantini: Financial Interests, Personal, Stocks/Shares, stock and/or other ownership interests: Labcorp Drug Development. L. Del Mastro: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Pfizer, Merck Sharp & Dohme, Genomic Health, Takeda, Ipsen, Eisai, Eli Lilly, Celgene, Pierre Fabre, Seagen, Daiichi Sankyo, Exact Sciences, Amgen. R. Berardi: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Novartis, Merck, Otsuka, Eli Lilly, Roche. C. Genova: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Roche, Sanofi, Takeda, ThermoFisher. All other authors have declared no conflicts of interest.
67P - Blood cell gene expression and clinical characteristics in advanced non-small cell lung cancer with immune-related adverse events
- L. Daniello (Heidelberg, Germany)
- L. Daniello (Heidelberg, Germany)
- M. Elshiaty (Heidelberg, Germany)
- F. Lusky (Heidelberg, Germany)
- M. Blasi (Heidelberg, Germany)
- M. A. Schneider (Heidelberg, Germany)
- F. Bozorgmehr (Heidelberg, Germany)
- R. Shah (Heidelberg, Germany)
- D. Kazdal (Heidelberg, Germany)
- A. Angeles (Heidelberg, Germany)
- S. Liersch (Heidelberg, Germany)
- F. Eichhorn (Heidelberg, Germany)
- M. Allgäuer (Heidelberg, Germany)
- F. Janke (Heidelberg, Germany)
- H. Bischoff (Heidelberg, Germany)
- M. Thomas (Heidelberg, Germany)
- H. Sültmann (Heidelberg, Germany)
- A. Stenzinger (Heidelberg, Germany)
- P. Christopoulos (Heidelberg, Germany)
Abstract
Background
Immune checkpoint inhibitors (ICI) have improved the prognosis of non-small-cell lung cancer (NSCLC) but can also cause immune-related adverse events (irAEs), which can be life-threatening and have a complex management. Currently, there is a need for molecular and clinical markers to predict irAEs occurrence and outcome.
Methods
Clinical characteristics of 762 patients with stage IV NSCLC receiving first- or second-line PD-(L)1 inhibitors were analyzed. Additionally, blood samples of 8 patients with irAEs were analyzed at baseline (BL) and at the time of toxicity (TT) in comparison with 8 matched control samples from patients with similar clinical characteristics and ICI exposure, but no irAEs. The expression of 12 genes involved in the immune response (GATA3, TBX21, MKI67, CD247, FAS, FASLv1, FOXP3, GzmB, IFNγ, PD1, PRF1, RORgt) was absolutely quantified in PAXgene blood RNA samples using RT-PCR and plasmid standards.
Results
IrAEs occurred in 176/762 cases (23%), with a similar frequency for ICI monotherapy or chemoimmunotherapy (24% vs. 22%). CTCAE severity was grade 1 in 11%, grade 2 in 41%, grade 3 in 37%, grade 4 in 10%, and 2 events were lethal (1%). Frequently affected were endocrine glands (21%), lungs (17%), musculoskeletal system (17%), colon (15%) and liver (15%). All other organs were less commonly affected (15%). IrAEs occurrence showed a significant association with a better ECOG performance status (28% vs. 18% for PS 0 vs. 1, p = 0.006), PD-L1 positivity (25% vs. 14%, p = 0.009), and a lower neutrophil-to-lymphocyte ratio (NLR, 28% vs. 19% with the median 6.2 as cut-off, p = 0.004). Blood cell gene expressions in patients with irAEs was slightly higher for 7/12 immunologically relevant genes at TT, and for 11/12 genes at BL, but not significantly different (p≥0.07). No substantial changes in gene expression were noted between BL and TT in each group (mean fold change for the irAEs group = 0.82, for the controls = 0.84, p ≥0.07).
Conclusions
IrAEs under PD-(L)1 inhibitors occur more frequently in patients with PD-L1-positive NSCLC, a better ECOG PS, and a lower NLR. No relationship between the blood expression of selected immunologically relevant genes and irAEs occurrence was noted.
Legal entity responsible for the study
Thoraxklinik Heidelberg.
Funding
German Center for Lung Research (DZL).
Disclosure
P. Christopoulos: Financial Interests, Institutional, Funding, outside the submitted work: AstraZeneca, Amgen, Merck, Novartis, Roche, Takeda; Financial Interests, Personal, Advisory Board, outside the submitted work: Boehringer Ingelheim, Chugai, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, Gilead, Novartis, Takeda; Financial Interests, Institutional, Funding, outside the submitted work.: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
68P - OncoMutational ratio on ctDNA: A potential novel biomarker in NSCLC
- P. Ambrosini (Milan, Italy)
- P. Ambrosini (Milan, Italy)
- L. Provenzano (Milan, Italy)
- A. Bottiglieri (Milan, Italy)
- A. Spagnoletti (Milan, Italy)
- G. Di Guida (Caserta, Italy)
- L. Mazzeo (Milan, Italy)
- T. Beninato (Milan, Italy)
- R. Leporati (Milan, Italy)
- M. Occhipinti (Milan, Italy)
- M. Brambilla (Milan, Italy)
- S. Manglaviti (Milan, Italy)
- M. Ganzinelli (Milan, Italy)
- V. Miskovic (Milan, Italy)
- C. Proto (Milan, Italy)
- A. Dumitrascu (Milan, Italy)
- F. De Braud (Milan, Italy)
- C. Della Corte (Napoli, Italy)
- G. Lo Russo (Milan, Italy)
- G. Viscardi (Napoli, Italy)
- A. Prelaj (Milan, Italy)
Abstract
Background
Emerging evidence proposed ctDNA as a noninvasive biomarker for multiple cancer-related objectives. NSCLC patients (pts) with negative post-treatment ctDNA have better outcomes compared to positive post-treatment ctDNA. Tumor mutational burden (TMB) has been offered as a predictive marker for immunotherapy (IOT), although its use in the clinical setting remains uncertain due to conflictual RCT data. This study evaluated the impact on survival of the mutation load ratio detected on liquid biopsy in aNSCLC pts.
Methods
We retrospectively calculated “OncoMutational Ratio” (OMR), defined as a fraction between the number of pathogenic mutations and the number of genes analysed of genomic panels, on aNSCLC pts who undergone liquid biopsy at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan and Luigi Vanvitelli Hospital in Naples from April 2017 to September 2022. Guardant360CDx® and Archer® LiquidPlex™ test were utilized. Patients with OMR value above the median value were defined high-OMR (h-OMR).
Results
456 patients had OMR status available on liquid biopsy, with a median value of 0.04545 (IQR 0.021–0.091). Patients with h-OMR were more frequently smokers and enriched with TP53 mutations. In the total population h-OMR was associated with worse OS (18.7 vs 28.4 m; HR 1.55, CI 95% 1.23–1.95; p < 0.001). OS was not significantly different among pts not treated with IOT (17.4 vs 19.4 m) (non-IOT-cohort), whereas a significant worse OS was observed among IOT-treated patients (18.9 vs 33.8 m, p for interaction <0.001) (IOT-cohort). Among patients treated with any-line IOT (N = 293) a trend for worse PFS was also observed in h-OMR, although without statistical significance (HR 1.24, CI 95% 0.97–1.58, p = 0.082). Notably, a trend to a decreased IOT-DCR was observed in h-OMR patients (69.7% vs 58.3%, p = 0.066), while no differences were observed in terms of ORR.
Conclusions
The present study demonstrated that a higher mutation load ratio detected on liquid biopsy significantly predicted survival in aNSCLC patients treated with standard therapies. This effect was mostly shown in IOT-cohort compared to non-IOT-cohort, suggesting h-OMR as a predictive potential biomarker. These results deserve to be validated in prospective studies to be used in clinical practice.
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale Tumori Milano.
Funding
Has not received any funding.
Disclosure
C. Proto: Financial Interests, Personal, Other: BMS, MSD. F.G.M. De Braud: Financial Interests, Personal, Invited Speaker: BMS, Healthcare Research & Pharmacoepidemiology, Merck Group, MSD, Pfizer, Servier, Sanofi, Roche, Amgen, Incyte, Dephaforum, Seagen, Novartis, F.Hoffmann-LaRoche Ltd, BMS, Ignyta Operating INC, Merck Sharp & Dohme Spa, Kymab, Pfizer, Tesaro, MSD, MedImmune LCC, Exelixis Inc, LOXO Oncology Incorporated, Daiichi Sankyo Dev. Limited, Basilea Pharmaceutica International AG, Janssen-Cilag International NV, Merck KGAA; Financial Interests, Personal, Other, Consultant Advisory Board: Roche, EMD Serono, NMS Nerviano Medical Science, Sanofi, MSD, Novartis, Incyte, BMS, Menarini, AstraZeneca, Pierre Fabre. C.M. Della Corte: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Sub investigator in clinical Trial: Merck; Financial Interests, Personal, Other, Sub-investigator in clinical trial: Roche. G. Lo Russo: Financial Interests, Personal, Advisory Board: MSD, Novartis, AstraZeneca, BMS, Pfizer, Roche, Sanofi; Financial Interests, Personal, Invited Speaker: Italfarmaco, Sanofi; Financial Interests, Institutional, Invited Speaker: BMS, MSD, GSK, Celgene, Novartis, Roche, AstraZeneca, Amgen. A. Prelaj: Financial Interests, Personal, Other, Training of personnel: AstraZeneca, Italfarma; Financial Interests, Personal, Invited Speaker, The Hive Project: Discussant: Roche; Financial Interests, Personal, Advisory Board, Advisory board in Lung Cancer project: BMS; Financial Interests, Personal, Other, Travel Grant: Janssen. All other authors have declared no conflicts of interest.
69P - The effect of inflammatory-nutritional prognostic scoring system (INPS) on treatment response and prognosis in patients with metastatic NSCLC as second-line treatment with nivolumab
- M. Keskinkiliç (Atlanta, United States of America)
- M. Keskinkiliç (Atlanta, United States of America)
- F. Yalcin Kucukbayrak (Izmir, Turkey)
- G. Polat (Izmir, Turkey)
- D. Delibalt (Izmir, Turkey)
- H. Ellidokuz (Izmir, Turkey)
- I. Oztop (Izmir, Turkey)
Abstract
Background
We aimed to reveal the predictive and prognostic value and biomarker of the novel scoring system, the inflammatory-nutritional prognostic score (INPS), on nutritional and immune status in patients with NSCLC who received second-line nivolumab therapy.
Methods
In this study, patients who were treated in Dokuz Eylul University, Department of Medical Oncology between October 2018 and September 2022, and who were diagnosed with metastatic NSCLC and received nivolumab as a second-line therapy were evaluated retrospectively. Demographic characteristics, blood tests, clinicopathological features of the tumor and information about the treatments they received were recorded. We selected the most valuable biomarkers to develop INPS by the least absolute shrinkage and selection operator (LASSO) Cox regression model. A prognostic nomogram incorporating INPS and other independent clinicopathological factors was developed based on the stepwise multivariate Cox regression method. Then, we evaluate the prognostic performance and predictive accuracy of the predictive nomogram.
Results
Using the LASSO Cox regression model, determining overall survival as primary endpoint, six inflammatory-nutritional biomarkers, namely, SII, NLR, PLR, MLR, PNI, and LAR, out of 8 (eliminated two inflamatory variables AAPR and CAR) have been selected and used to construct the INPS for 67 metastatic NSCLC cancer patients treated with nivolumab. Six of the eight inflammatory markers were shown to have a statistically significant prognostic value on overall survival and were included in the INPS nomogram. Using the cut-off points of these six inflammatory-nutritional biomarkers, the INPS scores (from 0 to 6) have been obtained. As a final step, the INPS scores are used to construct the risk groups (from low to high).
Conclusions
The search for prognostic markers other than PD-L1 and TMB is still ongoing in patients receiving immunotherapy. With this study, for the first time in the literature, the new screening system, INPS, created with various nutritional and inflammatory markers, has shown that it can be used as a prognostic tool in metastatic NSCLC patients receiving immunotherapy.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
70P - Impact of TP53/KRAS mutations on overall survival of metastatic non-small cell lung cancer patients (pts) treated with systemic first-line therapy
- S. Rubio Novella (Castellon de la Plana, Spain)
- S. Rubio Novella (Castellon de la Plana, Spain)
- A. Cobo (Castellón de La Plana, Spain)
- Á. Montes (Castellón de La Plana, Spain)
- J. Soler Lopez (Castellón de La Plana, Spain)
- M. Arnal Rondan (Castellón de La Plana, Spain)
- S. Noguera Palanca (Castellón de La Plana, Spain)
- I. Tena (Castellón de La Plana, Spain)
- J. Miguel (Castellón de La Plana, Spain)
- B. Navarro (Castellón de La Plana, Spain)
- I. Domingo (Castellón de La Plana, Spain)
- S. Cases Esteban (Castellón de La Plana, Spain)
- M. Díaz (Castellón, Spain)
- P. Andrade (Castellón, Spain)
- E. Rosello (Castellón, Spain)
- J. Lazaro Santander (Castellón, Spain)
- D. Lorente Estelles (Castellón de La Plana, Spain)
- A. Sanchez Hernandez (Castellón de La Plana, Spain)
Abstract
Background
Mutations in TP53 and KRAS are frequent in NSLC pts, particularly in non-squamous histology. Improved biomarkers for treatment selection are needed. We aimed to investigate the impact of TP53 and KRAS mutation on treatment outcome of pts with first-line systemic therapy for mNSCLC.
Methods
Single-institution retrospective cohort of mNSCLC pts treated with ≥1 line of systemic therapy. A targeted NGS panel (Oncomine Precision) including KRAS and TP53 was performed on all pts; actionable EGFR, ALK, ROS-1 alterations were excluded. PDL1 was assessed by IHC (SP263 Ab). The main objective was to study the association between TP53 and/or KRAS mutations and OS (overall population, and in PDL1 ≥ 50% and PDL1 < 50% populations). OS was defined as the time from therapy start to last visit or death. Kaplan-Meier method was used to calculate median OS; associations with OS were assessed through Cox-regression models.
Results
68 mNSCLC pts were included. Most had non-squamous histology (92.5%), ECOG PS 0–1 (81%) and PDL1 < 50% (81%). TP53 and KRAS mutations were observed in 34.3% and 23.9%, respectively; 3% had co-occurring mutations. 52% received chemo-immunotherapy combinations and 20% immunotherapy. Median OS was 9.8 months (95%CI: 6.8-NR). In the overall population, a non-significant trend was observed for higher OS in TP53-mutated pts (HR 0.5; p = 0.058). There was a significant OS benefit in TP53 mutated pts with PDL1 < 50% (HR: 0.44; 95%CI: 0.20–0.98; p = 0.043), but not in PDL1 ≥ 50% (HR 0.89; 95%CI: 0.10–7.7; p = 0.92) pts. No association between KRAS mutations and OS was observed (
| TP53 mutation | KRAS mutation | |||||
|---|---|---|---|---|---|---|
| Yes | No | HR (95%CI); pval | Yes | No | HR (95%CI); pval | |
| All pts | 18.4 m | 7.3 m | 0.50 (0.24–1.02); p = 0.058 | 7.3 m | 12.4 m | 1.5 (0.75–2.9); p = 0.25 |
| PDL1 < 50% | 18.4 m | 6.9 m | 0.44 (0.20–0.97); p = 0.043 | 8.9 m | 12.4 m | 1.3 (0.60–2.7); p = 0.49 |
Conclusions
We observed a statistically significant difference in OS favouring pts with TP53 mutations in the PDL1 < 50% population. No survival impact of KRAS mutations was observed. TP53 mutations could represent a potential biomarker for treatment selection for pts with low PDL1 expression treated with chemo-immunotherapy. Prospective validation is needed.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
71P - Biomarker analysis from phase I/II study of tusamitamab ravtansine (SAR408701) in patients with advanced non-small cell lung cancer (NSCLC)
- A. Gazzah (Villejuif, Cedex, France)
- A. Gazzah (Villejuif, Cedex, France)
- J. Lee (Cambridge, United States of America)
- E. Wang (Cambridge, United States of America)
- N. Ternès (Paris, France)
- H. Wang (Cambridge, United States of America)
- E. Boitier (Paris, France)
- A. Lartigau (Paris, France)
- M. Chadjaa (Paris, France)
- C. Dib (Paris, France)
- G. Muzard (Paris, France)
- S. Valence (Paris, France)
- A. Remaury (Paris, France)
- C. C. Palu (Cambridge, United Kingdom)
- A. Bauchet (Paris, France)
Abstract
Background
Tusamitamab ravtansine is an antibody-drug conjugate of a humanized carcinoembryonic antigen (CEA)-related cell adhesion molecule 5 (CEACAM5)-specific monoclonal antibody linked to DM4. A phase I/II study showed tusamitamab ravtansine antitumor activity in pretreated patients (pts) with advanced nonsquamous NSCLC and high CEACAM5 expression. Here, we explore biomarker associations with tumor CEACAM5 expression by immunohistochemistry (IHC), and whether biomarkers predict objective response rate (ORR).
Methods
We assessed CEACAM5 expression by IHC, RNA sequencing, and whole exome sequencing (WES) on latest archival tumor samples; and circulating CEACAM5 (cCEACAM5) and CEA (cCEA). We enrolled 2 cohorts of pts with IHC CEACAM5 membrane expression at ≥2+ intensity: in ≥50% of tumor cells (high expressors, HEs, n = 64); and in ≥1% to <50% of tumor cells (moderate expressors, MEs, n = 28). Pts received tusamitamab ravtansine 100 mg/m2 IV every 2 weeks.
Results
cCEA and cCEACAM5 were strongly associated (Spearman rho, 0.9), with weak associations between IHC CEACAM5 and cCEA or cCEACAM5 (Spearman rho, 0.3 and 0.4, respectively). Higher levels of CEACAM5 mRNA were observed in CEACAM5 HEs vs MEs (P = 0.0027). EGFR and KRAS genetic alterations by WES were present in 44.8% and 65.5% of CEACAM5 HEs, respectively, and 21.4% and 78.6% of CEACAM5 MEs, respectively. Confirmed partial responses were seen in 13/64 HEs (ORR 20.3%) and 2/28 MEs (ORR 7.1%). In CEACAM5 HEs with available baseline (BL) cCEA data, 25/62 (40.3%) had a cCEA level ≥100 µg/L, with a median value of 71.6 µg/L (range 1–8809); corresponding values in CEACAM5 MEs were 7/28 (25.0%) and 12.4 µg/L (range 0.5–684). In response evaluable CEACAM5 HEs with available BL cCEA data (n = 61), ORR was 10/24 (41.7%) in pts with high cCEA (≥100 µg/L) and 3/37 (8.1%) in pts with low cCEA (<100 µg/L); corresponding ORRs in CEACAM5 MEs were 0/7 and 2/21 (9.5%).
Conclusions
In CEACAM5 HEs, high cCEA was associated with numerically greater ORR vs low cCEA (41.7% vs 8.1%). Associations were also observed between: cCEA and cCEACAM5; IHC CEACAM5, cCEA, and cCEACAM5; and IHC CEACAM5 and CEACAM5 tumor mRNA levels, but not between IHC CEACAM5 and actionable oncogenic drivers.
Clinical trial identification
NCT02187848.
Editorial acknowledgement
Medical writing was provided by Michael Stillman and Julian Martins, inScience Communications and was funded by Sanofi.
Legal entity responsible for the study
Sanofi.
Funding
Sanofi.
Disclosure
J.S. Lee: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. E. Wang: Financial Interests, Personal, Full or part-time Employment: Sanofi. N. Ternès: Financial Interests, Personal, Full or part-time Employment: Sanofi. H. Wang: Financial Interests, Personal, Full or part-time Employment: Sanofi. E. Boitier: Financial Interests, Personal, Full or part-time Employment: Sanofi. A. Lartigau: Financial Interests, Personal, Full or part-time Employment: Sanofi. M. Chadjaa: Financial Interests, Personal, Full or part-time Employment: Sanofi. C. Dib: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. G. Muzard: Financial Interests, Personal, Full or part-time Employment: Sanofi. S. Valence: Financial Interests, Personal, Full or part-time Employment: Sanofi. A. Remaury: Financial Interests, Personal, Full or part-time Employment: Sanofi. C.C. Palu: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. A. Bauchet: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. All other authors have declared no conflicts of interest.
72P - Association of receptor activator of nuclear factor kappa-Β ligand (RANKL) and epidermal growth factor receptor (EGFR) gene expression with bone metastases (mets) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC)
- A. Brouns (Heerlen, Netherlands)
- A. Brouns (Heerlen, Netherlands)
- L. Hendriks (Maastricht, Netherlands)
- I. Robbesom-van den Berge (Rotterdam, Netherlands)
- A. Driessen (Maastricht, Netherlands)
- G. Roemen (Maastricht, Netherlands)
- B. Van Herpen (Maastricht, Netherlands)
- Z. Dekkers (Maastricht, Netherlands)
- B. Heitzer (Maastricht, Netherlands)
- D. Leunissen (Maastricht, Netherlands)
- L. Moonen (Maastricht, Netherlands)
- R. Lunde (Roermond, Netherlands)
- M. Westenend (Venlo, Netherlands)
- M. Van Driel (Rotterdam, Netherlands)
- E. M. Speel (Maastricht, Netherlands)
- A. C. Dingemans (Rotterdam, Netherlands)
Abstract
Background
Bone mets are frequent in NSCLC. The receptor activator of Nuclear Factor κB (RANK)/ RANKL/osteoprotegerin (OPG) pathway is important in bone mets development. EGFR signaling promotes osteoclast formation and stimulation. Understanding the biological mechanism of bone mets development might have implications for treatment strategies. We studied the association of EGFR, RANKL, RANK, OPG gene expression in tumor and presence of bone mets in mNSCLC.
Methods
Retrospective multicenter study (2008–2017), included: EGFR mutated (EGFR+), Kirsten rat sarcoma (KRAS+), EGFR/KRAS wildtype mNSCLC. Ribonucleic Acid was isolated from tumor samples and EGFR, RANK, RANKL, OPG gene expressions were determined via quantitative Polymerase Chain Reaction. Data on demographics, molecular subtyping, origin of pathology sample, presence/progression of bone mets, SREs were collected. Primary endpoint: relation between EGFR, RANK, RANKL, OPG gene expression, RANKL:OPG ratio and bone mets.
Results
n 169/335 (50%) pts tumor samples were available, in 73 (43%) gene expression analysis could be performed. 46/73 (63%) pts had bone mets at diagnosis/developed bone mets (
Baseline characteristics
| Characteristics | Total n = 73 |
|---|---|
| Female n (%) | 46 (63) |
| Never smoker n (%) | 8 (11) |
| Mean age at diagnosis metastatic NSCLC, years (range) | 62.8 (32–84) |
| Molecular subgroup n (%) | |
| EGFR+ | 23 (32) |
| KRAS+ | 36 (49) |
| EGFR/KRAS wildtype | 14 (19) |
| Origin of pathology sample n (%) | |
| Lung (primary tumor) | 29 (40) |
| Bone | 9 (12) |
| Other metastasis | 35 (48) |
| Metastatic disease at diagnosis n (%) | 47 (64) |
| Bone mets at diagnosis stage IV n (%) | 27 (37) |
| Bone mets at diagnosis or during course of disease n (%) | 46 (63) |
| SRE n (% of all pts with bone mets) | 26 (57) |
| Type of SRE n (% of all SREs) | |
| Radiotherapy | 25 (96) |
| Pathologic fracture | 4 (15) |
| Surgery | 6 (23) |
| Spinal cord compression | 2 (8) |
| BTA use in all pts n (%) | 9 (12) |
| Denosumab | 1 (1) |
| Bisphosphonate | 8 (11) |
Conclusions
Increased RANKL gene expression and RANKL:OPG ratio, but not EGFR expression, was associated with presence of bone mets. Increased RANKL:OPG gene ratio was associated with a higher incidence of bone mets development.
Legal entity responsible for the study
The authors.
Funding
The Five4Five Foundation, Cancer Research Fund Limburg (2018).
Disclosure
A. Brouns: Financial Interests, Personal, Advisory Board, Not related to the work submitted in the abstract: Janssen. L. Hendriks: Financial Interests, Institutional, Advisory Board: Amgen, Boehringer Ingelheim, Eli Lilly, Novartis, Pfizer, Takeda, BMS, Merck, Janssen, MSD; Financial Interests, Personal, Other, mentorship with key opinion leaders funded by AstraZeneca: AstraZeneca; Financial Interests, Institutional, Invited Speaker, for educational webinar: AstraZeneca, Eli Lilly; Financial Interests, Institutional, Invited Speaker, educational webinar/interview: Bayer; Financial Interests, Institutional, Invited Speaker, educationals: MSD; Financial Interests, Personal, Invited Speaker, for webinars: Medtalks; Financial Interests, Institutional, Advisory Board, one time also personal: Roche; Financial Interests, Institutional, Other, performing interviews at conference: Roche; Financial Interests, Personal, Other, travel support: Roche; Financial Interests, Institutional, Other, podcast on brain metastases: Takeda; Financial Interests, Personal, Invited Speaker, payment for post ASCO round table discussion: VJOncology; Financial Interests, Personal, Invited Speaker, payment for post ASCO/ESMO/WCLC presentations, educational committee member: Benecke; Financial Interests, Institutional, Invited Speaker, payment for post ESMO/ASCO discussion: high5oncology; Financial Interests, Institutional, Other, educational webinar: Janssen; Financial Interests, Personal, Other, member of the committee that revised these guidelines: Dutch guidelines NSCLC, brain metastases and leptomeningeal metastases; Financial Interests, Institutional, Research Grant, for IIS: Roche, Boehringer Ingelheim, AstraZeneca, Takeda; Financial Interests, Institutional, Invited Speaker: AstraZeneca, GSK, Novartis, Merck Serono, Roche, Takeda, Blueprint Medicines, Mirati, AbbVie, MSD, Gilead; Financial Interests, Institutional, Research Grant, donation for health care improvement project: Merck; Financial Interests, Institutional, Research Grant, funding for healthcare improvement project: Pfizer; Non-Financial Interests, Personal, Other, Chair metastatic NSCLC for lung cancer group: EORTC; Non-Financial Interests, Personal, Other, secretary NVALT studies foundation: NVALT. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Sanofi, Amgen, Bayer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Takeda, Eli Lilly, Janssen, Pfizer, AstraZeneca, Eli Lilly, Amgen, Daiichi Sankyo, Roche, JNJ, Mirati; Financial Interests, Institutional, Research Grant: Amgen; Non-Financial Interests, Personal, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Personal, Member: IASCL, ASCO, AACR. All other authors have declared no conflicts of interest.
73P - Qualitative research to evaluate perceptions around biomarker testing and patient-reported outcomes (PROs) for use in studies of non-small cell lung cancer (NSCLC)
- M. K. Horn (Phoenix, United States of America)
- M. K. Horn (Phoenix, United States of America)
- S. Mathias (Palm Beach Gardens, United States of America)
- H. Colwell (Palm Beach Gardens, United States of America)
- A. Heerdegen (Titusville, United States of America)
- K. Bevans (Titusville, United States of America)
- T. Li (Raritan, United States of America)
- A. Stevens (Titusville, United States of America)
- J. Sermon (Beerse, Belgium)
- J. Fastenau (Horsham, United States of America)
- R. Pierson (Raritan, United States of America)
Abstract
Background
Exon 19 deletion (19Del) and exon 21 point mutation (L858R) account for 85–90% of EGFR mutations in NSCLC and confer sensitivity to EGFR tyrosine kinase inhibitors. To evaluate the content validity and relevance of 4 PROs (NSCLC-SAQ, EORTC QLQ-C30, PROMIS-PF-8, TASQ) for use in clinical trials of this specific NSCLC population and understand perceptions of biomarker testing (BT), qualitative interviews were conducted.
Methods
ICAN, International Cancer Advocacy Network, helped identify study participants. Participants completed one Zoom interview containing concept elicitation and cognitive debriefing questions, guided by an interview guide, developed for this study. Interviews were recorded, transcribed, and analyzed using qualitative software. Symptoms/impacts were mapped to the PROs, and gap analysis was conducted. IRB approval was obtained.
Results
A total of 36 NSCLC adult patients with a confirmed diagnosis of advanced or metastatic 19Del or L858R NSCLC in the US, UK, Canada, Spain, and India were enrolled (mean age = 56, 81% female, 64% receiving 1st-line treatment, 92% with metastatic disease). Pain in areas other than the chest (69%), cough (67%), fatigue (64%), shortness of breath (58%), difficulty remembering/focusing (58%), and chest pain (33%) were the most common symptoms. Physical (35%), social (40%), and emotional (82%) impacts, and difficulty with daily activities (77%) were common. In general, patients found the PROs to be clear, comprehensive, and relevant. Gap analysis revealed the only concept missing was weight loss. All patients had undergone BT. 68% underwent BT at the time of diagnosis, biopsy, or surgery. 42% were unaware that BT was being done until after it had occurred. 79% reported BT was done to inform the targeted treatment decision, 96% felt results affected the type of treatment received, and 60% reported that they understood at least a little about the results. 78% would consider a timeframe of < 1 week to receive results as acceptable.
Conclusions
Findings provide evidence to support the content validity, clarity, and relevance of the four PROs in a population with EGFR-mutated NSCLC. Patients understand the value of BT.
Legal entity responsible for the study
Health Outcomes Solutions.
Funding
Janssen Global Services LLC.
Disclosure
S.D. Mathias: Financial Interests, Institutional, Research Grant: Health Outcomes Solutions. H. Colwell: Financial Interests, Institutional, Research Grant: Health Outcomes Solutions. A.C. Heerdegen: Financial Interests, Personal, Stocks/Shares: Janssen. K. Bevans: Financial Interests, Personal, Stocks/Shares: Janssen. T. Li: Financial Interests, Personal, Stocks/Shares: Janssen. A. Stevens: Financial Interests, Personal, Stocks/Shares: Janssen. J. Sermon: Financial Interests, Personal, Stocks/Shares: Janssen. J. Fastenau: Financial Interests, Personal, Stocks/Shares: Janssen. R. Pierson: Financial Interests, Personal, Stocks/Shares: Janssen. All other authors have declared no conflicts of interest.
74P - Non-small cell lung cancer (NSCLC) predictors of response to immunotherapy (ICI): LIPI index and immune-related toxicity
- A. Moratiel Pellitero (Zaragoza, Spain)
- A. Moratiel Pellitero (Zaragoza, Spain)
- M. Zapata García (Zaragoza, Spain)
- M. Zurera Berjaga (Zaragoza, Spain)
- I. Ruiz Moreno (Zaragoza, Spain)
- A. Goás Gómez (Zaragoza, Spain)
- M. Martí Pi (Zaragoza, Spain)
- A. Romero Monleón (Zaragoza, Spain)
- K. Osorio (Zaragoza, Spain)
- M. Arribas Velasco (Zaragoza, Spain)
- S. Esteras Per (Zaragoza, Spain)
- M. Gascon Ruiz (Zaragoza, Spain)
- A. Sesma Goñi (Zaragoza, Spain)
- E. Quilez Bielsa (Zaragoza, Spain)
- M. Isla Casado (Zaragoza, Spain)
Abstract
Background
ICI is proposed as the standard treatment for metastatic NSCLC in first-line and subsequent indications. It has different adverse effects with respect to traditional antineoplastics, given the stimulation of the immune system. Objective: analyze whether patients with a good prognosis lung cancer immunotherapy prognostic index (LIPI) have a better response to ICI and also to evaluate the relation of immune-related adverse events (irAEs) and response in patients with NSCLC in real clinical practice.
Methods
Observational, retrospective, single-center study. Cohort of stage IV NSCLC patients between 2016 and 2021. Toxicity grade (1–4) according to The Common Terminology Criteria for Adverse Events version 4.0. Response assessment according to RECIST 2.0 and immuno-related criteria. ICI in first (65%) or second (35%) line. Descriptive and survival analysis. Degree of toxicity and response to treatment (overall results and according to treatments and histology). LIPI index and response. LIPI defined as: dNLR (absolute neutrophil count/[white blood cell count − absolute neutrophil count]) ≥3 and lactate dehydrogenase (LDH) greater than the upper limit of normal; stratifies patients in “good” (G), “intermediate” (I) and “poor” (P) prognostic groups.
Results
N = 168 patients (p) (130 men/38 woman). Mean age 64.3 years. Mean dNLR 2.46. Average LDH 244U/L. Response: 15 (9%) complete response (CR), 50 (30%) partial response (PR), 39 (22%) stable disease (SD), 45 (28%) progression disease (PD) and 19 (11%) not evaluated (NE). 114 deaths (56% G, 76% I, 93% P). PFS (G 19 months, I 6, P 2) and OS (G 27 months, I 8, P 3). Adenocarcinoma 116 [77 with irAES G1-4 (13 CR, 31 PR, 21 SD, 8 PD, 4 NE), 39 without (3 PR, 6 SD, 21 PD, 9 NE]. Squamosus 52 [27 with irAES G1-4 (2 CR, 12 PR, 9 SD, 4 PD), 25 without (4 PR, 3 SD, 12 PD, 6 NE).] irAES appearance: longer PFS (19 vs 2 months) and OS (27 vs 4 months) p < 0.0001.
Conclusions
Good prognosis LIPI score patients (dNRL<3 and normal LDH) present a better response to ICI. LIPI index is a positive predictor of response to ICI. The presence of irAES is related with a better immune system response. In contrast, the absence of toxicity predicts a worse prognosis.
Legal entity responsible for the study
Medical Oncology Department, Hospital Clínico Universitario Lozano Blesa.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
75TiP - A multicenter, open-label, phase II trial evaluating the safety and efficacy of folate receptor alpha (FRα) antibody-drug conjugate (ADC) farletuzumab ecteribulin (FZEC*) in patients with previously treated, metastatic non-small cell lung cancer (NSCLC) adenocarcinoma (AC)
- D. Planchard (Villejuif, France)
- D. Planchard (Villejuif, France)
- L. Paz-Ares (Madrid, Spain)
- A. Spira (Fairfax, United States of America)
- E. Felip (Barcelona, Spain)
- S. McCune (Marietta, United States of America)
- T. Cascella (Princeton, United States of America)
- J. Dennie (Princeton, United States of America)
- P. Bhagavatheeswaran (Princeton, United States of America)
- C. Dumitru (Nutley, United States of America)
- H. Borghaei (Philadelphia, United States of America)
Abstract
Background
There is an unmet therapeutic need for patients with NSCLC who have disease progression after standard of care treatment. FRα is highly expressed on tumor cells in patients with NSCLC AC. FZEC is an ADC comprised of the humanized anti-FRα monoclonal antibody farletuzumab and the microtubule dynamics inhibitor eribulin. A phase I study in Japan (NCT03386942) demonstrated the antitumor activity of FZEC across multiple tumor types, including NSCLC, and identified interstitial lung disease (ILD) as an adverse event of interest (Shimizu 2021). This global, multicenter, phase II trial across 6 countries aims to evaluate the safety, efficacy, and optimal dose of FZEC in patients with previously treated metastatic NSCLC AC.
Trial design
Approximately 60 adults with advanced/metastatic NSCLC either without genetic alterations who have received ≥ 1 line of platinum-doublet chemotherapy and anti–PD-1/PD-L1 therapy or with genetic alternations who have received 1 targeted therapy and ≤ 3 lines of systemic therapy will be enrolled. Patients will be randomized 1:1 to receive FZEC Q3W at doses of 33 mg/m2 (Arm A) or 25 mg/m2 (Arm B). A pharmacokinetics model demonstrated that body surface area (BSA)–based dosing is predicted to reduce the risk of exposure-driven ILD (Hayato 2022). The primary objectives are to assess incidence of treatment-related adverse events leading to study discontinuation and investigator-assessed objective response rate by RECIST v1.1. Primary analysis will be performed after ≥ 6 months follow-up. Safety follow-up will occur 30 days after last dose, with survival follow-up every 3 months from safety follow-up visit until last participant has completed 2 years of follow-up. Measures to enhance early detection of ILD have been introduced and steps to potentially reduce the occurrence of severe ILD include implementation of BSA–based dosing, lung-specific eligibility criteria, revised and stringent ILD management criteria, and ILD training for relevant study personnel. *Formerly MORAb-202.
Clinical trial identification
NCT05577715.
Editorial acknowledgement
Editorial support was provided by Emily Motola, PharmD, and Richard McDonald of Spark Medica Inc.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
D. Planchard: Financial Interests, Personal, Advisory Role, Consultancy fees: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, Roche, Janssen, AbbVie; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, Roche, Janssen, AbbVie; Financial Interests, Personal, Principal Investigator, Principal or Co-investigator: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, Janssen, AbbVie; Financial Interests, Personal, Other, Travel/accommodation support: AstraZeneca, Roche, Novartis, Pfizer. L. Paz-Ares: Financial Interests, Personal and Institutional, Funding, Grants: MSD, AstraZeneca, Pfizer, and Bristol Myers Squibb and consulting fees from Eli Lilly, MSD, Roche, PharmaMar, Merck KGaA (Darmstadt, Germany), AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GlaxoSmithKline, Janssen, Takeda; Financial Interests, Personal, Other, Honoraria: Roche/Genentech, Eli Lilly, Pfizer, Bristol Myers Squibb, MSD, AstraZeneca, Merck Serono, PharmaMar, Novartis, Celgene, Amgen, Mirati, AbbVie; Financial Interests, Personal, Other, Meeting attendance/travel: Roche, AstraZeneca, MSD, Bristol Myers Squibb, Eli Lilly, Pfizer; Financial Interests, Personal, Advisory Board, Data safety monitoring, advisory board: Altum Sequencing and Genomica; Financial Interests, Personal, Advisory Board, External board: Genomica; Financial Interests, Personal, Ownership Interest, Founding partner: Altum Sequencing; Financial Interests, Personal, Other, Other financial interests: Novartis, Ipsen, Pfizer, Servier, Sanofi, Roche, Amgen, and Merck. A. Spira: Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol Myers Squibb, Bayer, Inctye, Amgen, Novartis, Mirati Therapeutics, Gritstone Oncology, Gritstone Bio, Jazz Pharmaceuticals, Takeda, Janssen Research & De; Financial Interests, Institutional, Other, Honoraria: Array BioPharma, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb, and Blueprint Medicines; Financial Interests, Personal, Funding: LAM Therapeutics and Regeneron; Financial Interests, Institutional, Funding: Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, LAM Therapeutics, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therap. E. Felip: Financial Interests, Institutional, Funding: Merck; Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Sanofi, Takeda, Bergenbio; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medica Trends, Medscape, Merck Serono, Merck Sharp & Dohme, Peervoice, Pfizer, Sanofi, Takeda, Touch Oncology; Financial Interests, Personal, Member of the Board of Directors, Independent board member: Grifols. S. McCune: Financial Interests, Personal, Other, Consulting fees, honoraria: Bristol Myers Squibb. T. Cascella: Financial Interests, Personal, Full or part-time Employment: Myers Squibb; Financial Interests, Personal, Stocks/Shares: Myers Squibb; Financial Interests, Personal, Other, Meeting attendance support: Myers Squibb. J. Dennie: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. P. Bhagavatheeswaran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. C. Dumitru: Financial Interests, Personal, Full or part-time Employment: Eisai Inc. H. Borghaei: Financial Interests, Personal, Funding: Bristol Myers Squibb, Eli Lilly, and Amgen; Financial Interests, Personal, Advisory Board, Also consulting: Bristol Myers Squibb, Eli Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Amgen, Axiom, PharmaMar, Takeda, Mirati, Daiichi Sankyo, Guardant, Natera, Oncocyte, BeiGene, iTEO, Jazz Pharmaceuticals, Janssen, Da Vo; Financial Interests, Personal, Other, Honoraria: Amgen, Pfizer, Daiichi Sankyo, and Regeneron; Financial Interests, Personal, Other, Meeting/travel support: Amgen, Bristol Myers Squibb, Merck, Eli Lilly, EMD-Serano, Genentech, and Regenero; Financial Interests, Personal, Advisory Board, Data safety monitoring board: University of Pennsylvania CAR T program, Takeda, Incyte, and Novartis; Financial Interests, Personal, Other, Medical writing support: Bristol Myers Squibb, Amgen, and AstraZeneca; Financial Interests, Personal, Stocks/Shares: Sonnetbio, Inspirna, Rgenix, and Nucleai.
76TiP - Fecal microbiota transplantation to improve efficacy of immune checkpoint inhibitors in metastatic lung cancer
- I. Massalha (Beer Sheva, Israel)
- I. Massalha (Beer Sheva, Israel)
- A. Segal (Beer sheva, Israel)
- M. T. Moskovitz (Petah Tikva, Israel)
- A. Yakobson (Beer sheva, Israel)
- R. Zabit (Beer Sheva, Israel)
- S. M. Stemmer (Petah Tikva, Israel)
- W. Shalata (Beer Sheva, Israel)
- Y. Dudnik (Beer Sheva, Israel)
- G. Markel (Petah Tikva, Israel)
- N. Geva-Zatorsky (Haifa, Israel)
- A. Meirovitz (Beer Sheva, Israel)
Abstract
Background
Immunotherapy has recently become a main-stream treatment option in cancer care, with improved clinical outcomes in many malignancies, especially that of lung cancer. The long-term benefits of this treatment however are limited. Thus, there is a critical need to distinguish predictive biomarkers of response from those of resistance, and to develop synergistic strategies for improved therapeutic response. Strong emerging evidence indicates that the gut microbiome has the ability to influence response to immunotherapy. Unlike tumor genomics, the gut microbiome is modifiable, and thus, its modulation to enhance response to immunotherapy is an attractive therapeutic strategy. The main objective of this study is to evaluate the safety and efficacy of Fecal Microbiota Transplant (FMT) in altering response to immunotherapy in patients with metastatic lung cancer. The overall goal is to determine microbiome compositional and gene-content changes in patients who respond more efficiently to immunotherapy subsequent to FMT. This understanding may lead to future microbiome-based treatments combined with immunotherapy to significantly increase the efficacy of lung cancer treatment. In this prospective clinical-and molecular study, we will perform an in-depth analysis of the potential role of FMT in the context of immunotherapy.
Trial design
This prospective, stratified, randomized, placebo-controlled, double-blinded, comparative study. The study will assess the feasibility of Fecal microbiome transplant (FMT) when used in conjunction with standard immunotherapy +/- chemotherapy as a first-line treatment for metastatic lung cancer to enhance the disease control rate. Completely respond metastatic patients to immunotherapy will serve as the fecal implant donors. Patients will start receiving placebo/antibiotics then receive placebo/FMT on the first day of the (chemo-)immunotherapy cycle 1 and then every 3 weeks. The FMT capsules and (chemo-)immunotherapy administrations will be repeated until End of Treatment.
Clinical trial identification
NCT05502913.
Legal entity responsible for the study
I. Massalha.
Funding
Israel Cancer Association.
Disclosure
N. Geva-Zatorsky: Financial Interests, Personal, Leadership Role: Biotax Labs LTD. All other authors have declared no conflicts of interest.
77TiP - A phase I/II dose escalation and dose expansion study of ozuriftamab vedotin (BA3021) alone and in combination with nivolumab in patients with advanced solid tumors including non-small cell lung cancer
- M. Alexander (Mount Pleasant, United States of America)
- M. Alexander (Mount Pleasant, United States of America)
- A. Starodub (Cincinnati, United States of America)
Abstract
Background
Ozuriftamab vedotin (BA3021) is a conditionally active biologic (CAB) anti-receptor tyrosine kinase orphan receptor 2 (ROR2) humanized monoclonal antibody (IgG1) conjugated to monomethyl auristatin E (MMAE) using a cleavable linker (CAB ROR2 ADC). Preclinical data suggest targeting ROR2 may result in antitumor activities in various tumor types, such as NSCLC. Taken together with the proposed mechanism of BA3021 and underlying biology, antitumor activity in NSCLC is anticipated. The upregulation of ROR2 in PD-1 resistant tumor strongly suggests its role in resistance and recurrence in this population.
Trial design
BA3021-001 is a multi-center, open-label, phase I/II study designed to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of BA3021 alone and in combination with nivolumab in patients with advanced solid tumors. Phase I will comprise 2 sequential parts—dose escalation and dose expansion—and is designed to evaluate the safety and tolerability of BA3021 in patients with advanced solid tumors and to identify the MTD and/or RP2D for BA3021. Phase II is an open-label study to evaluate the efficacy and safety of BA3021 alone and in combination with nivolumab in patients with ROR2-expressing tumor membrane percent score ≥ 1%, metastatic NSCLC, or melanoma who have measurable disease by RECIST version 1.1 criteria and have documented progression according to RECIST v1.1 criteria within the 6 months prior to enrollment. NSCLC patients must have experienced failure, defined as disease progression or discontinuation due to an adverse event, of a PD-1/L-1, epidermal growth factor receptor (EGFR) inhibitor, or anaplastic lymphoma kinase (ALK) inhibitor (either monotherapy or in combination with another therapy such as ipilimumab). Enrollment completion is anticipated in 2023.
Clinical trial identification
NCT04681131; EudraCT 2022-000135-23.
Legal entity responsible for the study
BioAtla, Inc.
Funding
BioAtla, Inc.
Disclosure
M. Alexander: Financial Interests, Personal, Principal Investigator: BioAtla. A. Starodub: Financial Interests, Personal, Principal Investigator: BioAtla.
78TiP - Phase Ib/IIa safety and tolerability study of bemcentinib with pembrolizumab/carboplatin/pemetrexed in subjects with untreated advanced or metastatic non-squamous NSCLC with/without STK11 mutations
- R. Veluswamy (New York, United States of America)
- R. Veluswamy (New York, United States of America)
- S. Bhalla (Dallas, United States of America)
- R. Mehra (Baltimore, United States of America)
- O. Gligich (Miami, United States of America)
- M. C. Garassino (Chicago, United States of America)
- C. Oliva (Oxford, United Kingdom)
- C. Gorcea-Carson (Oxford, United Kingdom)
- N. McCracken (Oxford, United Kingdom)
Abstract
Background
The combination of platinum chemotherapy, pemetrexed and pembrolizumab (CIT) has become a standard of care as first-line (1L) treatment in patients with non-squamous NSCLC. Despite improvements in response rates and survival, the emergence of primary or acquired resistance limits its efficacy. Serine/threonine kinase 11 mutations (STK11m) are common (˜20%) in NSCLC and promote immune suppression by activation of AXL signalling. Bemcentinib (BEM), a selective AXL inhibitor, has been shown in preclinical studies to sensitize STK11m NSCLC to pembrolizumab. Therefore, the addition of BEM to CIT has the potential to improve the 1L treatment outcomes of NSCLC, particularly in tumors harboring STK11m.
Trial design
This is an open-label, multi-center, phase Ib/IIa clinical study to assess the safety, tolerability, and preliminary anti-tumor activity of BEM in combination with CIT as 1L treatment in patients with advanced (stage IIIb/IIIc) or metastatic (stage IV) non-squamous NSCLC without actionable mutations. In the phase IIa, patients with a STK11 mutation will be enrolled. All patients will receive BEM orally on Day 1 of each 21-day CIT treatment cycle. After the completion of 4 cycles of CIT + BEM, patients will receive maintenance with BEM + pemetrexed + pembrolizumab. Phase Ib follows a 3+3 design. Patients will receive BEM + CIT at one of 3 daily BEM dose levels: Cohort 1 = 75 mg; Cohort 2 = 100 mg; or Cohort 3 = 150 mg. An independent data safety monitoring board will review the safety data from each cohort at the end of the dose-limiting toxicity assessment period (the first 21 days of cycle 1 for each patient of each cohort) and will recommend the BEM dose for the phase IIa expansion. The study consists of a screening period (up to 28 days), a treatment period (up to 24 months) and overall survival follow up for each subject for at least 2 years. Up to 24 and 40 patients will be enrolled in the phase Ib and IIa, respectively. The trial is currently enrolling patients in the phase Ib in the US; patients’ recruitment for the phase IIa is planned to open in Q2 2023 in Europe, UK, and US.
Clinical trial identification
EudraCT 2019‐003806‐28/NA/124645.
Legal entity responsible for the study
BerGenBio Ltd, UK.
Funding
BerGenBio.
Disclosure
R. Veluswamy: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb, AstraZeneca, Merck, Boehringer Ingelheim, BerGenBio, Merus, Novocure, G1 Therapeutics, Regeneron; Financial Interests, Personal, Other, Steering Committee: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, consulting honorarium: BeiGene; Non-Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, Onconova,, AstraZeneca, Boehringer Ingelheim, Lung Cancer Research Foundation, Stand Up 2 Cancer. S. Bhalla: Financial Interests, Personal, Advisory Board: Takeda. R. Mehra: Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Advisory Board: Rakuten Medical, Coherus, Janssen. M.C. Garassino: Financial Interests, Personal, Advisory Board: AstraZeneca, MDS International GmBH, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda, Seattle Genetics, Mirati, Daiichi Sankyo, Regeneron, Merck, Ose Immuno Therapeutics, Blueprint, Janssen, Sanofi; Financial Interests, Institutional, Invited Speaker: Eli Lilly, MDS, Pfizer, AstraZeneca, MDS International GmBH, BMS, Boehringer Ingelheim Italia S.p.A., Celgene, Eli Lilly, Ignyta, Incyte, MedImmune, Novartis, Pfizer, Roche, Takeda, Tiziana, Foundation Medicine, GSK, Spectrum Pharmaceuticals; Other, Institutional, Other: AIRC, AIFA, Italian MoH, TRANSCAN, research fundings, Horizon 2020. C. Oliva: Financial Interests, Institutional, Full or part-time Employment: BerGenBio. C. Gorcea-Carson: Financial Interests, Institutional, Full or part-time Employment: BerGenBio. N. McCracken: Financial Interests, Institutional, Full or part-time Employment: BerGenBio. All other authors have declared no conflicts of interest.
79TiP - Progress of a phase I trial (TOTEM) of repotrectinib in combination with osimertinib in advanced, metastatic EGFR mutant NSCLC
- A. Aguilar Hernandez (Barcelona, Spain)
- A. Aguilar Hernandez (Barcelona, Spain)
- M. Cobo (Málaga, Spain)
- A. Azkarate (Mallorca, Spain)
- A. Calles (Madrid, Spain)
- M. Gonzalez Cao (Barcelona, Spain)
- A. Cantero (Málaga, Spain)
- J. Terrasa (Mallorca, Spain)
- R. Alvarez (Madrid, Spain)
- M. Molina (Barcelona, Spain)
- R. Rosell (Badalona, Spain)
Abstract
Background
Osimertinib has robust efficacy as first-line treatment for advanced EGFR mutant non-small cell lung cancer (NSCLC). Osimertinib with repotrectinib inhibited Src/FAC/Janus kinase 2 (JAK2), STAT3 and YAP1 signaling, abrogating tumor growth, and having efficacy with no substantial toxicity in patients (pts) with EGFR-mut tumors. Based on this evidence, we designed the current trial. The TOTEM trial will evaluate the tolerability/safety, preliminary efficacy, the pharmacokinetic (PK) and pharmacodynamic (PD) profile of repotrectinib and osimertinib.
Trial design
Eligible pts are ≥ 18 years, diagnosed with locally advanced, unresectable or metastatic NSCLC harboring EGFR exon 18, exon 19, exon 21, or T790M mut, ECOG 0-1, either without brain metastasis (BM) or asymptomatic BM, and creatinine clearance >50 mL/min. Treatment with previous chemotherapy, immunotherapy, and tyrosine kinase inhibitors (TKIs), including osimertinib, is allowed. The study includes an initial dose escalation phase following a 3+3 design to determine the recommended phase II dose (RP2D). Pts receive osimertinib monotherapy for 14 days at 80 mg per day (QD), followed by osimertinib in combination with repotrectinib at the assigned dose level (80 mg QD, 160 QD, or 160 mg twice a day [bid]); The expansion phase will enroll 20–30 pts who have progressed to osimertinib or first /second-generation TKIs, who will receive the combination at the RP2D. Treatment will continue until progression, or unacceptable toxicity. Tolerability is evaluated by the incidence of dose-limiting toxicities (DLTs). The RP2D is defined as the dose level with less than 33% of pts experiencing a DLT. Safety is assessed by frequency and severity of adverse events. Secondary endpoints include objective response rate, intracranial response (for pts with BM), PFS, and OS. As of Jan 2023, 11 pts are accrued. No DLT was reported at 80 mg QD of repotrectinib, while 1/6 pts had a DLT consisting of renal toxicity at 160 mg QD. Preliminary PKs results showed no significant interaction that required dose adjustments. The third dose level (160 mg bid repotrectinib/80 mg osimertinib) is currently open to recruitment and 2 pts have already initiated study treatment.
Clinical trial identification
NCT04772235, EudraCT 2020-005151-20.
Editorial acknowledgement
We acknowledge MFAR Clinical Research staff for their assistance in the development of this abstract.
Legal entity responsible for the study
Instituto Oncológico Dr. Rosell (IOR).
Funding
IOR though industry partner Bristol-Myers Squibb (BMS).
Disclosure
All authors have declared no conflicts of interest.
80TiP - High-dose aumolertinib versus osimertinib in EGFR T790M+ NSCLC patients with brain metastases (ATTACK)
- S. Lu (Shanghai, China)
- S. Lu (Shanghai, China)
- L. Han (Xuzhou, China)
- D. Lv (Taizhou, China)
- Z. Zhang (Hefei, China)
- J. Wu (Haikou, China)
- Q. Wang (Zhengzhou, China)
- X. Dong (Wuhan, China)
- Y. Hu (Wuhan, China)
- J. Chen (Changsha, China)
- L. Wu (Changsha, China)
Abstract
Background
Third-generation EGFR-TKIs have demonstrated superior CNS efficacy compared with first-generation EGFR-TKIs or chemotherapy in previous phase III studies (AENEAS, FLAURA, AURA3). However, there is a lack of head-to-head comparison of CNS efficacy between third-generation EGFR-TKIs. Herein, we conduct the ATTACK study to evaluate the efficacy and safety of aumolertinib compared with osimertinib in EGFR T790M+ NSCLC patients with brain metastases.
Trial design
ATTACK is a multicenter, open-label, randomized, controlled trial. Patients with histologic or cytologic confirmation of advanced NSCLC and are known to have progression of radiologic disease on first- or second-generation EGFR-TKIs and harbor an EGFR T790M mutation are eligible. At baseline, patients are required to have at least one measurable intracranial lesion, defined as ≥10 mm. Approximately 232 patients will be randomized (1:1) to receive either 165 mg aumolertinib or 80 mg osimertinib, administered once daily orally, stratified by the type of EGFR mutation (Ex19del or L858R). Treatment continues in 21-day cycles until disease progression, withdrawal of consent, the development of unacceptable side effects, or the fulfillment of other discontinuation criteria. The primary endpoint is intracranial progression free survival (iPFS). Secondary endpoints include PFS, objective response rate (ORR), disease control rate (DCR), intracranial ORR (iORR), intracranial DCR (iDCR), overall survival (OS), and safety. Adverse effects are graded per CTCAE v.5.0. The first patient had been enrolled in November 2022.
Clinical trial identification
NCT04870190.
Legal entity responsible for the study
Shanghai Chest Hospital.
Funding
Jiangsu Hansoh Pharmaceutical Group Co., Ltd.
Disclosure
S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Boehringer Ingelheim, Hutchison MediPharma, Simcere Pharmaceutical Group, Zai Lab, GenomiCare, Yuhan, Prime Oncology, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Hansoh Pharma, Hengrui Therapeutics; Financial Interests, Personal, Research Grant: AstraZeneca (Inst), Hutchison MediPharma (Inst), BMS (Inst), Hengrui Therapeutics (Inst), BeiGene (Inst), Roche (Inst). All other authors have declared no conflicts of interest.
81TiP - NVL-655, a selective anaplastic lymphoma kinase (ALK) inhibitor, in patients with advanced ALK-positive solid tumors: The phase I/II ALKOVE-1 study
- M. L. Johnson (Nashville, United States of America)
- M. L. Johnson (Nashville, United States of America)
- S. Ou (Orange, United States of America)
- E. Felip (Barcelona, Spain)
- C. Baik (Seattle, United States of America)
- B. Besse (Villejuif, France)
- J. Mazieres (Toulouse, France)
- D. Camidge (Aurora, United States of America)
- S. Gadgeel (Detroit, United States of America)
- A. Drilon (New York, United States of America)
- Y. Y. Elamin (Houston, United States of America)
- G. Liu (Toronto, Canada)
- J. Reuss (Washington, United States of America)
- T. Kehrig (Cambridge, United States of America)
- H. Pelish (Cambridge, United States of America)
- V. Zhu (Cambridge, United States of America)
- J. J. Lin (Boston, United States of America)
Abstract
Background
Aberrations of the ALK oncogene drive tumor cell proliferation, survival, and metastasis in multiple adult and pediatric cancers. ALK gene fusions are detected in ∼5% of advanced non-small cell lung cancers (NSCLC); among these patients, the incidence of central nervous system (CNS) metastases at diagnosis is ∼40%. Although 5 tyrosine kinase inhibitors (TKIs) are approved by the FDA and EMA for ALK-positive NSCLC, therapeutic limitations remain, such as acquired resistance due to secondary and compound ALK mutations and/or neurologic adverse events attributed to off-target inhibition of TRK. NVL-655 is a novel, brain-penetrant ALK-selective TKI that exhibits preclinical activity against diverse ALK fusions and mutations, including G1202R and G1202R compound mutations, while sparing inhibition of TRK. The ALKOVE-1 study is evaluating the safety and preliminary activity of NVL-655 in patients with solid tumors harboring oncogenic ALK alterations, including those with acquired ALK resistance mutations and CNS metastases.
Trial design
ALKOVE-1 consists of a phase I dose escalation followed by a phase II expansion in cohorts defined by tumor type and prior therapies. Phase I includes adult patients with any solid tumor type harboring an oncogenic ALK gene fusion or activating mutation (by local testing), including ALK fusion-positive NSCLC after ≥ 1 prior 2nd or 3rd generation ALK TKI. Prior platinum-based chemotherapy and/or immunotherapy, CNS disease without progressive neurological symptoms or increasing corticosteroid doses, and evaluable but non-measurable disease are allowed. Patients will receive NVL-655 by daily oral administration. Primary phase I objectives are to determine the NVL-655 recommended phase II dose and, if applicable, maximum tolerated dose. Additional objectives include evaluation of safety/tolerability, preliminary activity, and characterization of the pharmacokinetic and pharmacodynamic profiles of NVL-655. Longitudinal analysis of circulating tumor DNA will be performed, including ALK mutation profiling and other relevant biomarkers. The phase I portion of the study is ongoing.
Clinical trial identification
NCT05384626 (May 20, 2022).
Legal entity responsible for the study
Nuvalent, Inc.
Funding
Nuvalent. Inc.
Disclosure
M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Calithera Biosciences, Carisma TherapeuticsEQRx, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Exelixis, Fate Therapeutics, Immunitas Therapeutics, Kartos Therapeutics, Merus, Palleon Pharmaceuticals, Syndax Pharmaceuticals, Dracen Pharmaceuticals, Dynavax, Eli Lilly, Elicio Therapeutics, EMD Serono, Erasca, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn, Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Mirati Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, and Y-mAbs Therapeutics; Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera, Checkpoint Therapeutics, CytomX, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Molecular Axiom, Novartis, Pyramid Biosciences, Revolution Medicines, SeaGen, Takeda Pharmaceuticals, VBL Therapeutics, Gritstone Oncology, Ideaya Biosciences, iTeos, Janssen, Eli Lilly, Merck, Mirati Therapeutics, Oncorus, Regeneron Pharmaceuticals, Ribon Therapeutics, Sanofi-Aventis, Turning Point Therapeutics. S.I. Ou: Financial Interests, Personal, Ownership Interest: Turning Point Therapeutics, Elevation Oncology; Financial Interests, Personal, Advisory Board: Elevation Oncology; Financial Interests, Personal, Other, corporate-sponsored research: Pfizer, Daiichi Sankyo, Revolution Medicine, Merus, Roche, Mirati, BluePrint Medicines, JNJ/Janssen; Financial Interests, Personal, Other: JNJ/Janssen, BeiGene, Pfizer, Eli Lilly, DAVA Oncology LLP, Caris Life Science. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Merck Sharp & Dohme, Pfizer, Sanofi, Takeda, Merck Serono, Peptomyc, F. Hoffmann-La Roche, Novartis, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono, Sanofi, Takeda, TouchONCOLOGY; Financial Interests, Institutional, Other, Grant for Oncology Innovation: Merck Healthcare KGAa; Financial Interests, Institutional, Other, Fundación Merck Salud: Fundación Merck Salud; Financial Interests, Personal, Invited Speaker, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc, Exelixis Inc, Merck KGAA, Janssen-Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc, Bristol-Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc; Non-Financial Interests, Personal, Leadership Role, President (2021–2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). C. Baik: Financial Interests, Institutional, Principal Investigator: Rain Oncology, AbbVie, Nuvalent, Blueprint, TurningPoint, Eli Lilly, AstraZeneca, Janssen, Daiichi Sankyo, Spectrum, Pfizer, Loxo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Boehringer Ingelheim, Janssen, Regeneron, Silverback, Pfizer, AstraZeneca, Guardant, TurningPoint, Takeda. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Genzyme Corporation, Chugai pharmaceutical, EISAI, Inivata, Ipsen, Turning Point Therapeutics. J. Mazieres: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Pfizer, Jiangsu Hengruii, Blueprint, Daiichi Sankyo, Novartis, Amgen; Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Pierre Fabre, BMS. S. Gadgeel: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Genentech/Roche, Bristol Myers Squibb, Pfizer, Novartis, Blueprint, Daiichi Sankyo, Mirati, Eli Lilly, Merck, Esai, Blueprint, GSK; Financial Interests, Personal, Other, Data Safety Monitoring Board: AstraZeneca. A. Drilon: Financial Interests, Personal, Advisory Board: Ignyta/Genentech/Roche, Loxo/Bayer/Eli Lilly, Takeda/Ariad/Millennium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, BeiGene, BerGenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem Oncology, MORE Health, AbbVie, 14ner/Elevation Oncology, Remedica Ltd., ArcherDX, Monopteros, Novartis, EMD Serono, Melendi, Liberum, Repare RX, Amgen, Janssen, EcoR1, Monte Rosa; Financial Interests, Personal, Other, CME: Medscape, Onclive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, PeerView Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, Med Learning, Imedex, Answers in CME, Medscape, Clinical Care Options, AiCME; Financial Interests, Personal, Other, CME, Consulting: Axis; Financial Interests, Personal, Other, Consulting: Nuvalent, Merus, EPG Health, mBrace, Harborside Nexus, Ology, TouchIME, Entos, Treeline Bio, Prelude, Applied Pharmaceutical Science, Inc; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Remedica Ltd, RV More; Financial Interests, Personal, Stocks/Shares: Treeline Biosciences; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, stocks: mBrace; Financial Interests, Institutional, Funding, Research funding: Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, PharmaMar; Financial Interests, Personal, Funding, Research: Foundation Medicine; Non-Financial Interests, Personal, Member: ASCO, AACR, IASLC; Other, Personal, Other, Food/Beverage: Merck, PUMA, Merus; Other, Personal, Other, Other: Boehringer Ingelheim. G. Liu: Financial Interests, Personal and Institutional, Advisory Board: Pfizer, Takeda, AstraZeneca, Amgen, EMD Serono, Merck, Jazz Pharmaceuticals, Novartis, Eli Lilly, Roche; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, Takeda, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Pfizer, Takeda, AstraZeneca, Amgen, Boehringer Ingelheim; Financial Interests, Personal and Institutional, Funding: Pfizer, Takeda, AstraZeneca, Amgen; Financial Interests, Personal and Institutional, Principal Investigator: Pfizer, Takeda, AstraZeneca; Financial Interests, Personal and Institutional, Speaker's Bureau: EMD Serono. J.E. Reuss: Financial Interests, Institutional, Research Grant: Genentech/Roche, Verastem, Nuvalent, Mesothelioma Applied, Research Foundation, LUNGevity Foundation, MedStar Health Institute; Financial Interests, Personal, Advisory Board: Sanofi/Genzyme, Genentech/Roche, Personalis, Guardant, AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck. T. Kehrig: Financial Interests, Personal, Full or part-time Employment: Nuvalent, Inc.; Financial Interests, Personal, Stocks/Shares: Nuvalent, Inc. H.E. Pelish: Financial Interests, Personal, Full or part-time Employment: Nuvalent, Inc.; Financial Interests, Personal, Stocks/Shares: Nuvalent, Inc. V. Zhu: Financial Interests, Personal, Full or part-time Employment: Nuvalent, Inc.; Financial Interests, Personal, Stocks/Shares: Nuvalent, Inc. J.J. Lin: Financial Interests, Personal, Other, Consulting: Turning Point Therapeutics, Nuvalent, Elevation Oncology, C4 Therapeutics, Bayer, Novartis, Mirati Therapeutics; Financial Interests, Personal, Advisory Board, Consulting: Blueprint Medicines, Genentech; Financial Interests, Personal, Other, Honorarium, travel: Pfizer; Financial Interests, Institutional, Invited Speaker: Turning Point Therapeutics, Neon Therapeutics, Relay Therapeutics, Bayer, Elevation Oncology, Roche/Genentech, Novartis, Hengrui Therapeutics, Pfizer, Nuvalent. All other authors have declared no conflicts of interest.
82TiP - A modular, open-label, phase I/II study to evaluate the safety, tolerability, pharmacokinetics and efficacy of EP0031, a next generation selective RET inhibitor, in patients with advanced RET-altered malignancies
- A. G. Gianoukakis (LA, United States of America)
- A. G. Gianoukakis (LA, United States of America)
- S. M. Arnold (Lexington, United States of America)
- S. A. Kahn (Stanford, United States of America)
- M. Taylor (Southfield, United States of America)
- E. Garralda (Barcelona, Spain)
- M. G. Krebs (Manchester, United Kingdom)
- H. Arkenau (London, United Kingdom)
- L. Clark (London, United Kingdom)
- G. Fisher (London, United Kingdom)
- V. Subbiah (Houston, United States of America)
Abstract
Background
Addressing resistance to 1st generation (gen) selective RET inhibitors (SRIs) is an area of high unmet need, with a number of RET dependent and independent pathways identified1,2. The ideal profile of a next gen SRI has been proposed: broad activity against RET fusions/mutations, inhibition of both V804M/L gatekeeper and G810C/S/R solvent front mutations and penetration of the CNS to address brain metastases1,2. This trial is evaluating whether EP0031, an orally available next gen SRI, can address resistance to 1st gen SRIs and improve on their clinical profile.
Trial design
This phase I/II study is recruiting up to 265 patients with NSCLC, thyroid cancer or other solid tumours with RET aberrations. The 1st part of the study is a dose escalation to investigate safety, tolerability, PK and PD and to define the maximum tolerated dose (MTD) and/or Recommended Phase II Dose (RP2D). Dose escalation is based on a rolling 6 design and is expected to recruit up to 40 patients. Once an RP2D is established, expansion cohorts of approximately 25 evaluable patients each will further explore the safety and tolerability of EP0031, and provide preliminary efficacy data in selected patient populations with RET-altered tumours with/without prior 1st gen SRI therapy: Four cohorts of patients with NSCLC and medullary thyroid cancer Two cohorts of patients with other solid tumours, including differentiated thyroid cancer. Key inclusion criteria are as follows: Male or female ≥ 18 years of age, with a diagnosis of an advanced solid tumour with documented RET altered malignancy ECOG Performance Status of 0 or 1 at screening with no deterioration over the previous 2 weeks. For expansion cohorts patients must have a solid tumour measurable by RECIST v1.1, with/without asymptomatic, stable brain metastases Recruitment was initiated in the US in November 2022 and is expanding to centres across Europe. A parallel phase I/II trial is ongoing in China (A400, NCT05265091, Kelun Biotech).
1Annals of Oncology 32(2) 261 (2021).
2Journal Thoracic Oncol 15(4) 542 (2020).
Clinical trial identification
NCT05443126.
Legal entity responsible for the study
Ellipses Pharma.
Funding
Ellipses Pharma.
Disclosure
A.G. Gianoukakis: Non-Financial Interests, Institutional, Writing Engagements: ATA Medullary thyroid cancer guidelines writing group; Non-Financial Interests, Institutional, Principal Investigator: Ellipses Pharma. S.M. Arnold: Non-Financial Interests, Institutional, Principal Investigator: Ellipses Pharma. S.A. Kahn: Non-Financial Interests, Institutional, Principal Investigator: Ellipses Pharma; Financial Interests, Personal and Institutional, Advisory Board, Also receives speaker fees: Eisai, Foundation Medicine. M. Taylor: Financial Interests, Personal and Institutional, Advisory Board, Also a speaker's role and receives research funding: Bristol Myers Squibb, Eisai Inc, Merck; Financial Interests, Personal and Institutional, Advisory Board: Novartis, Pfizer, Bayer, Sanofi/Genzyme, Regeneron, LOXO oncology, Exelixis, Cascade Prodrug; Financial Interests, Personal and Institutional, Advisory Board, Also a speaker's role: Blueprint Medicines; Financial Interests, Personal and Institutional, Advisory Board, Also receives research funding: Immune-Onc Therapeutics; Non-Financial Interests, Institutional, Principal Investigator: ISA Therapeutics, Simcha; Non-Financial Interests, Personal and Institutional, Principal Investigator: Ellipses Pharma. E. Garralda: Financial Interests, Personal, Advisory Board: Genentech, F.Hoffmann/La Roche, Neomed Therapeutics1 Inc, Boehringer Ingelheim, Janssen Global Services, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Eli Lilly, Hengrui; Financial Interests, Personal, Invited Speaker: Ellipses Pharma, Seattle Genetics, Bristol-Myers Squibb, MSD, F-Star Therapeutics; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho. M.G. Krebs: Financial Interests, Personal, Advisory Board: Bayer, Roche, Janssen, Guardant Health; Financial Interests, Personal, Invited Speaker: Roche, Janssen; Financial Interests, Institutional, Expert Testimony: AstraZeneca; Financial Interests, Institutional, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Blueprint, Astex, Bayer, BerGenBio, Carrick, Immutep, Janssen, Novartis, Nurix, Nuvalent, Pyramid Biosciences, Roche, Seattle Genetics, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Novartis; Other, Personal, Other, Travel expenses for congress: Immutep, Janssen. H. Arkenau: Financial Interests, Personal and Institutional, Full or part-time Employment, Has stock options: Ellipses Pharma. L. Clark: Financial Interests, Personal and Institutional, Full or part-time Employment, Holds stock options: Ellipses Pharma; Financial Interests, Personal, Stocks/Shares: Autolus Pharma. G. Fisher: Financial Interests, Personal and Institutional, Full or part-time Employment, Has stock options: Ellipses Pharma. V. Subbiah: Financial Interests, Personal, Advisory Board, One time advisory board: Incyte, Novartis, Eli Lilly/ Loxo Oncology; Financial Interests, Personal, Advisory Board, One time ad board: Roche, Pfizer; Financial Interests, Personal, Advisory Board, Ad hoc advisory board: Relay Therapeutics; Financial Interests, Institutional, Invited Speaker, Research funding to conduct Clinical trial: Eli Lilly/Loxo Oncology,, Blueprint medicines, Novartis, Boston Pharmaceuticals, Pfizer, Turning Point Therapeutics, Amgen, Bayer, Roche/ Genentech, Exelixis, Berg Pharma, N W Biotherapeutics, Relay Therapeutics, AbbVie, Agensys, Inhibrx, Dragonfly therapeutics, Takeda; Financial Interests, Institutional, Invited Speaker, Research funding to conduct clinical trial: Shasqi; Other, Personal, Other, I am employed at the University of Texas MD Anderson Cancer Center: The University of Texas MD Anderson Cancer Center; Other, Personal, Other, I receive research funding from NCI: National Cancer Institute, USA.
83TiP - A phase II study of mecbotamab vedotin (BA3011), a CAB-AXL-ADC, alone and in combination with nivolumab in adult patients with metastatic NSCLC who had prior disease progression on or are intolerant to a PD-1/L1, EGFR, or ALK inhibitor
- G. Dy (Buffalo, United States of America)
- G. Dy (Buffalo, United States of America)
- M. Alexander (Mount Pleasant, United States of America)
- D. Camidge (Aurora, United States of America)
Abstract
Background
Mecbotamab vedotin (BA3011) is a conditionally active biologic (CAB) anti-AXL antibody-drug conjugate being developed as an anticancer therapy for patients with advanced solid tumors. Conditional and reversible binding by CABs is designed to reduce off-tumor toxicity and immunogenicity, avoid tissue-mediated drug disposition, and improve pharmacokinetics. AXL is a cell-surface transmembrane receptor protein tyrosine kinase highly expressed in several tumor types including sarcoma. Increased AXL expression has been associated with tumor resistance to chemotherapy, programmed death-1 (PD-1) inhibitors, molecular targeted therapy, and radiation therapy. The upregulation of AXL in PD-1 resistant tumor strongly suggests its role in resistance and recurrence in this population. Additionally, as patients who have experienced failure of either an epidermal growth factor receptor (EGFR), or anaplastic lymphoma kinase (ALK) inhibitor have been shown to achieve minimal benefit with subsequent exposure to PD-1 monotherapy, there is considerable additional rationale for use of BA3011-based therapy.
Trial design
Study BA3011-002 is an ongoing multi-center, open-label, phase II trial designed to evaluate the efficacy and safety of BA3011 alone or in combination with nivolumab in patients with AXL-expressing (tumor membrane percent score ≥ 1%), metastatic NSCLC who have measurable disease by RECIST version 1.1 criteria. To enroll, patients must have experienced failure of an approved programmed death1/ligand-1(PD-1/L1) treatment, epidermal growth factor receptor (EGFR), or anaplastic lymphoma kinase (ALK) inhibitor (either monotherapy or in combination with another therapy such as ipilimumab). Treatment failure is defined as disease progression on a PD-1/L1, EGFR, or ALK inhibitor, or discontinuation of a PD-1/L1, EGFR, or ALK inhibitor due to an adverse event. Enrollment completion is anticipated in 2023.
Clinical trial identification
NCT04681131, EudraCT 2022-000135-23.
Legal entity responsible for the study
BioAtla, Inc.
Funding
BioAtla, Inc.
Disclosure
G. Dy: Financial Interests, Personal, Other, Consulting/honoraria: Amgen, AstraZeneca, Eli Lilly, Mirati, Regeneron, Takeda; Financial Interests, Personal, Principal Investigator: BioAtla. M. Alexander: Financial Interests, Personal, Principal Investigator: BioAtla. D.R. Camidge: Financial Interests, Personal, Advisory Role, Scientific Review Committee: Appolomics; Financial Interests, Personal, Advisory Role, ILD Adjudication Committee: AstraZeneca/Daiichi Sankyo, Mersana; Financial Interests, Personal, Advisory Role, DSMB: BeiGene; Financial Interests, Personal, Other, Consultancy: EMD Serono, Medtronic, Mirati, Onkure, Roche; Financial Interests, Personal, Principal Investigator: AbbVie, Pfizer, Dizal, Verastem, Karyopharm, Turning Point Therapeutics, Promontory Therapeutics, BioAtla.
85P - The impact of adjuvant EGFR-TKIs and 14-gene molecular assay on patients with stage I non-small cell lung cancer harboring sensitive EGFR mutations
- Y. Jiang (Guangzhou, China)
- Y. Jiang (Guangzhou, China)
- Y. Lin (Guangzhou, China)
- W. Fu (Guangzhou, China)
- R. Zhong (Guangzhou, China)
- Q. He (Guangzhou, China)
- J. He (Guangzhou, China)
- W. Liang (Guangzhou, China)
Abstract
Background
Currently, the role of EGFR-TKIs as adjuvant therapy for stage I, especially IA NSCLC, after surgical resection remains unclear. We aimed to compare the effect of EGFR-TKIs versus observation on survival in such patients by incorporating an established 14-gene molecular assay for risk stratification.
Methods
From March 2013 to February 2019, completely resected stage I (8th TNM staging for NSCLC) non-squamous NSCLC patients with sensitive EGFR mutation, who were followed up for at least five years, were included. Patients with eligible samples for molecular risk stratification were subjected to the 14-gene prognostic assay. The 5-year disease-free survival (DFS) rates between patients who underwent EGFR-TKI treatment and observation were compared using Kaplan-Meier analysis and Cox regression with a propensity score matching (PSM). The results of the 14-gene assay were used to further stratify the effect of EGFR-TKIs in different risk groups.
Results
A total of 227 stage I NSCLC patients were enrolled, with 110 in stage IA and 117 in stage IB. After PSM, a matched cohort with 96 (48:48) patients was generated. The median duration of follow-up was 78.9 months. In the overall population, patients with adjuvant EGFR-TKIs had better 5-year DFS rates than those in the observation group (97.9% vs. 81.3%; P = 0.008). For patients with IA NSCLC, those receiving EGFR-TKIs had favorable 5-year DFS rates (100.0% vs. 88.2%; P = 0.485); a same trend was obtained from IB group (96.8% vs. 77.4%; P = 0.053). The 14-gene assay was performed in 71 patients. In the observation group, patients in high-risk group had inferior DFS compared with those with intermediate (HR = 3.48, P = 0.192) and low-risk group (HR = 12.50, P = 0.024). Among intermediate-high-risk patients, EGFR-TKIs were associated with a significant trend in 5-year DFS rate benefit compared to observation (95.2% vs. 68.8%; P = 0.066), while there was no difference among low-risk group (100.0% vs. 89.5%; P = 0.492).
Conclusions
We showed that adjuvant EGFR-TKI might improve DFS of EGFR-mutated stage IA and IB NSCLC, and the 14-gene molecular assay could help enrich those benefits from treatment. This modality merits prospective interventional trials in the future.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
86P - KRAS G12C mutation and risk of disease recurrence in stage I surgically resected lung adenocarcinoma
- D. Marinelli (Rome, Italy)
- D. Marinelli (Rome, Italy)
- E. Melis (Rome, Italy)
- A. Torchia (Rome, Italy)
- D. Forcella (Rome, Italy)
- A. Botticelli (Rome, Italy)
- P. Visca (Rome, Italy)
- S. Buglioni (Rome, Italy)
- F. Facciolo (Rome, Italy)
- F. Gallina (Rome, Italy)
Abstract
Background
KRAS G12C mutations are found in about 12–13% of LUAD samples and it is unclear whether they are associated with worse survival outcomes in resected, early stage LUAD. We evaluated a retrospective, single-center cohort of patients treated with video-assisted thoracoscopic surgery (VATS) or robot-assisted thoracoscopic surgery (RATS) at our institution and leveraged on publicly available cohorts (TCGA LUAD, MSK LUAD604) to confirm the findings.
Methods
IRE cohort: retrospective cohort of patients with surgically resected, pathological stage I LUAD whose tumor tissue underwent targeted sequencing. TCGA LUAD cohort: pathologic stage I LUAD; patients who received post-operative radiation therapy and patients exposed to non-curative surgical resection were not included. MSK LUAD604 cohort: pathologic stage I LUAD. Clinical and genomic data for the TCGA LUAD and MSK LUAD604 cohort were downloaded from cBioPortal. The pooled cohort was made up by merging eligible patients in the IRE stage I cohort, TCGA LUAD stage I cohort and MSK LUAD604 stage I cohort.
Results
In the IRE stage I cohort we found a significant association between KRAS G12C mutations and worse DFS in multivariate analysis (DFS HR 2.47). In the TCGA LUAD stage I cohort we did not find any statistically significant association between the KRAS G12C mutation and survival outcomes. In the MSK LUAD604 stage I cohort we found that KRAS G12C mutated tumors had worse survival outcomes only when compared to KRAS nonG12C mutated tumors in univariate analysis (DFS HR 3.5). In the pooled stage I cohort (IRE stage I, TCGA LUAD stage I and MSK LUAD604 stage I tumors) we found that KRAS G12C mutated tumors had worse DFS when compared to KRAS nonG12C mutated tumors (DFS HR 2.6), to KRAS wild type tumors (DFS HR 1.6) and to any other tumors (DFS HR 1.8) in univariate analysis; in multivariable analysis, the KRAS G12C mutation was associated with worse DFS (DFS HR 1.61).
Conclusions
Our results suggest that patients with resected, stage I LUAD with a KRAS G12C mutation may have inferior survival outcomes when compared to KRAS nonG12C mutated tumors and to KRAS wild type tumors.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
87P - Prognostic models of recurrence free survival in non-small cell lung cancer
- K. R. Palmer (London, United Kingdom)
- K. R. Palmer (London, United Kingdom)
- A. Houston (London, United Kingdom)
- H. Macpherson (London, United Kingdom)
- W. Wang (London, United Kingdom)
- F. Quartly (London, United Kingdom)
- M. Grant (London, United Kingdom)
- K. R. Patel (London, United Kingdom)
- A. Ghose (London, United Kingdom)
- S. Williams (London, United Kingdom)
- L. Lim Farah (London, United Kingdom)
- J. Conibear (London, United Kingdom)
- K. Giaslakiotis (London, United Kingdom)
- K. Lau (London, United Kingdom)
- W. Ricketts (London, United Kingdom)
- A. Januszewski (London, United Kingdom)
Abstract
Background
Accurate prediction of recurrence-free survival (RFS) in patients undergoing radical surgery for early-stage non-small cell lung cancer (NSCLC) is necessary to improve outcomes. We aimed to develop pre- and post-operative prognostic models based on a range of clinicopathological factors using machine learning.
Methods
Retrospective data was collected from patients treated with radical surgery from 2015 to 2021, and 66 clinicopathological features were extracted. Three regularised Cox models were trialled (Ridge, LASSO and Elastic Net) and features were selected using a ‘maximum relevancy-minimum redundancy’ approach. Model development and validation were performed using nested cross-validation. Performance was assessed using the Concordance Index (C-index), Cumulative Dynamic Area Under the Receiver Operating Characteristic Curve (AUROC) and Dynamic Brier Score.
Results
392 patients were included; 145 (37%) patients developed recurrence or died from all causes, and median RFS was 74 months. The Elastic Net model – trained using systemic inflammatory response index [SIRI], eosinophil count, pre-operative nodal stage, weight loss, performance status and maximum standardized uptake value (SUVmax) – and the Ridge model – using performance status, weight loss, SIRI, eosinophil count, lymphovascular invasion, visceral pleural invasion, and pathological stage – proved optimal for pre- and post-operative prognosis, respectively (
| Model | Regularisation | N Features | C-Index | Mean AUROC | Mean Brier Score |
|---|---|---|---|---|---|
| Pre-surgical | Elastic Net | 6 | 0.70 ± 0.03 | 0.72 ± 0.02 | 0.18 ± 0.05 |
| Post-surgical | Ridge | 7 | 0.75 ± 0.04 | 0.79 ± 0.02 | 0.16 ± 0.04 |
Both models had better performance at predicting earlier recurrence or death with a pre-surgical and post-surgical 1-year AUROC of 0.73 ± 0.03 and 0.83 ± 0.08 respectively.
Conclusions
Our prognostic models demonstrate robust prediction of RFS in early-stage NSCLC, and may identify patients who will benefit from peri-operative anti-cancer therapy and/or closer post-operative surveillance. Future work is required to validate these models externally and prospectively.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
88P - Quantitative CT parameters in predicting the degree of risk of solitary pulmonary nodules
- L. Jiang (Shanghai, China)
- L. Jiang (Shanghai, China)
- S. Jiang (Shanghai, China)
- Q. Luo (Shanghai, China)
Abstract
Background
Correctly determining the degree of invasiveness based on histological pattern is markedly important in developing effective treatment strategies. Analyzing the characteristics of SPNs is quite important. The aim of our study, therefore, was to investigate the value of CT parameters in predicting the degree of risk.
Methods
Patients with clinical stage 0 to IB NSCLC who underwent radical surgical resection and were pathologically diagnosed with invasive adenocarcinoma were enrolled. All patients in this study underwent preoperative high-resolution CT scans with three-dimensional reconstruction. The minimum, maximum, and mean HU values were measured and recorded by Dr. Wise Lung Analyser on preoperative CT scans. All pathology specimens were centrally reviewed.
Results
The mean age was 57.4 ± 10.2 years old (median age was 57 years old), and 228 (64.2%) were females. A total of 355 SPNs were evaluated. CT findings revealed 71 pure GGO lesions (20.0%), 206 part-solid GGO lesions (58.0%), and 78 solid lesions (22.0%). In univariate logistic regression analysis, CT value max, CT value min, CT value mean, CT findings, and clinical stage were significantly related to high-risk SPN. The CT value mean and CT findings were independent significant factors on multivariate analysis. The receiver operating characteristic area under the curve used to identify low- or high-risk SPNs was 0.811.
Conclusions
The CT value mean and CT findings were independently correlated with high-risk SPN in multivariate analysis and are likely to be helpful for decisions on the therapeutic regimen, especially the appropriate extent of surgical resection.
Editorial acknowledgement
This paper was edited for English language by American Journal Experts (AJE).
Legal entity responsible for the study
The authors.
Funding
National Natural Science Foundation of China 81702251, 81972176 Natural Science Foundation of Shanghai 18ZR1435100 Nurture Projects for Basic Research of Shanghai Chest Hospital 2021YNJCQ3 Shanghai Hospital Development Center SHDC12016113 Shanghai Municipal Health Commission 20214Y0418 Shanghai Talent Development Fund 2021068 Talent training plan of Shanghai Chest Hospital Wu Jieping Medical Foundation 320.6750.2020-15-6.
Disclosure
All authors have declared no conflicts of interest.
89P - A clinical- and biological-based nomogram to predict unforeseen nodal metastases in clinically node-negative, radically resected lung adenocarcinoma
- F. Gallina (Rome, Italy)
- F. Gallina (Rome, Italy)
- F. Cecere (Rome, Italy)
- R. Tajè (Rome, Italy)
- D. Forcella (Rome, Italy)
- L. Landi (Rome, Italy)
- G. Minuti (Rome, Italy)
- S. Buglioni (Rome, Italy)
- P. Visca (Rome, Italy)
- E. Melis (Rome, Italy)
- I. Sperduti (Rome, Italy)
- F. Cappuzzo (Rome, Italy)
- F. Facciolo (Rome, Italy)
Abstract
Background
Despite an adequate preoperative staging, unexpected nodal metastases after surgery are detected in a relevant number of cases. Given the promising role of novel neoadjuvant treatments, the definition of predictive factors for nodal metastases is critical. In this study we aim to analyze the clinical and molecular factors associated with upstaging in patients with early stage LUAD without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy.
Methods
Patients who underwent radical treatment for early stage LUAD without evidence of nodal disease at the preoperative staging with available molecular targets evaluation were evaluated. Univariable and multivariable logistic regression was used to quantify the association between clinical and biological variables and the risk of unforeseen nodal metastasis, in addition to odds ratios and their 95% confidence intervals. A nomogram to predict unexpected nodal metastasis was computed based on the results of the multivariable model.
Results
A total of 359 patients were included. The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the PD-L1 status, ALK rearrangement, number of resected lymph nodes and the tumor diameter. This result was confirmed in the multivariate analysis, with an OR of 8.052 (3.123–20.763, p = 0.00001) for ALK rearrangements, 1.895 (1.093–3.286, p = 0.02) for PD-L1 status, 1.087 (1.048–1.127, p = 0.0001) for the number of resected nodes and 1.817 (1.214–2.719, p = 0.004) for cT status. Using the nomogram, we classified the patients into three classes: the lower risk group with a rate of unexpected nodal metastasis of 13.6% the intermediate group with a rate of 33.6% and the high group with a rate of 81.8%.
Conclusions
Our results showed that in patients with clinical node-negative early stage LUAD the presence of ALK rearrangements, PD-L1 status, number of resected lymph nodes and tumor diameter can predict unforeseen nodal metastasis after surgical resection. The established nomogram could assess the risk of nodal metastases in patients with early stage NSCLC eligible for surgical resection.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
90P - Cell-free DNA as a predictive and prognostic marker in adjuvant-treated non-small cell lung cancer
- E. AZKONA (Barakaldo, Spain)
- E. AZKONA (Barakaldo, Spain)
- R. Casas (Barcaldo, Spain)
- J. Aurrekoetxea (Barcaldo, Spain)
- I. De Elejoste Echebarria (San Sebastian (Donostia), Spain)
- M. Fernandez (Barcaldo, Spain)
- J. Azcuna Sagarduy (Barakaldo, Spain)
- L. García (Barcaldo, Spain)
- M. Saiz (Barcaldo, Spain)
- B. Ortega Gallastegi (Barcaldo, Spain)
- B. Calvo (Barcaldo, Spain)
Abstract
Background
There is a correlation of genomic alterations between tumor tissue and circulating cell-free DNA (cfDNA) in blood samples, mostly in advanced stages of cancer. The main objective of this study was the characterization of cfDNA of patients with non-small cell lung cancer (NSCLC) stages I–III before the adjuvant treatment (at the time of surgical intervention) and in those who relapse, with next generation sequencing (NGS). It was expected that the results could determine the changes that occur in cfDNA during treatment, follow-up and relapse.
Methods
Two blood samples were collected from each patient (before surgery and at relapse) and a paraffin tissue sample from the surgical specimen. cfDNA from blood plasma was sequenced using the 50-gene Oncomine Pancancer Assay panel. DNA obtained from tissues was analyzed with the 50-gene Oncomine Focus Assay panel.
Results
This prospective study included 73 patients with NSCLC of whom 22 met inclusion criteria (adjuvant treatment after surgery). The mean age was 63.36 years with a male/female ratio of 2.44. The concentrations of cfDNA were 1.42 ± 0.55, 1.57 ± 1.58 and 1.03 ± 0.45 ng/µl for stages I, II and III respectively with no significant differences. To date, two of the 22 patients have relapsed. The mean ratio of the cfDNA concentration (time of relapse/time of surgery) was 2.96. In the patient 1, no genetic variants were found in the three samples analyzed. The first liquid biopsy of patient 2 carried the p.R249S mutation in the TP53 gene and a 1.5-fold increase in CCND2 gene dosage. At the time of relapse, the allelic frequency of p.R249S alteration augmented from 3 to 40% and a 2.5-fold increase in CCND2 gene dosage was observed.
Conclusions
The use of liquid biopsy in early stages and the follow-up of patients with NSCLC is a potential tool for detecting tumor recurrence, as demonstrated by the increase in cfDNA concentration, mutated allele frequency and gene dosage after relapse. A long-term follow-up is required to assess the consistency and robustness of results.
Legal entity responsible for the study
Hospital Universitario Cruces- Biocruces Bizcaia Health Research Institute.
Funding
EITB Maratoia (BIO19/CP/003).
Disclosure
All authors have declared no conflicts of interest.
91P - Treatment (tx) patterns and outcomes in resectable early-stage non-small cell lung cancer (NSCLC): A global real-world (rw) study
- S. Lin (Cambridge, United States of America)
- S. Lin (Cambridge, United States of America)
- S. Nagar (Research Triangle Park, United States of America)
- M. Ahn (Seoul, Korea, Republic of)
- R. Affi (Mont de Marsan, France)
- J. Agulnik (Montreal, Canada)
- J. Shih (Taipei, Taiwan)
- M. J. Hochmair (Vienna, Austria)
- A. Tufman (Munich, Germany)
- D. Debieuvre (Mulhouse, France)
- J. Chow (London, United Kingdom)
- M. Jimenez (Research Triangle Park, United States of America)
- K. Davis (Research Triangle Park, United States of America)
- M. Sandelin (Molndal, Sweden)
- R. Veluswamy (New York, United States of America)
Abstract
Background
Complete resection ± adjuvant chemotherapy is recommended for most patients (pts) with early-stage (I–IIIA) NSCLC; however, 5-year overall survival (OS) rates for this regimen decrease with advancing disease stage. Osimertinib is a third-generation, EGFR-tyrosine kinase inhibitor approved as adjuvant tx for resected stage IB–IIIA EGFR mutated (EGFRm) NSCLC, based on the ADAURA trial results. We report final results from a global retrospective chart review of electronic health records (EHRs) for pts with resected stage IA–IIIA NSCLC, to show EGFRm frequency, tx patterns and outcomes prior to osimertinib approval.
Methods
Adults (≥18 yrs) with completely resected stage IA–IIIA NSCLC with available EGFRm results, who were diagnosed between 01Jan2014–31Dec2017, were assessed from diagnosis (Dx) until last follow-up/death. Primary endpoints included EGFRm frequency, tx patterns and OS. Sites of 1st recurrence was a secondary endpoint.
Results
EHRs were collected from 1243 pts in 8 countries. Of 530 pts (43%) with EGFRm NSCLC (pt characteristics,
| Characteristic, n (%) | Pts with EGFRm (n = 530) |
|---|---|
| Median age, yrs (range) | 64 (36–85) |
| Male | 183 (35) |
| Country | 84 (16) |
| Smoker | 19 (4) |
| Early-stage Histology at Dx in ≥1% | 513 (98) |
| Stage | 186 (35) |
| EGFRm in >2% | 219 (41) |
| PD-L1 | 178/530 (34) |
Conclusions
In this rw international study of pts with completely resected stage IA–IIIA EGFRm NSCLC, diagnosed between 2014 and 2017, 5-year landmark OS probabilities decreased from 94% to 46% from stage IA to IIIA. Early Dx and EGFR testing to inform optimal tx may improve outcomes in this population.
Editorial acknowledgement
The authors would like to acknowledge Laura Crocker, BMedSci (hons), of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP) guidelines.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
S. Lin: Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Personal, Stocks/Shares: Meta, Apple, Google, Amazon, Tesla, Rivian; Financial Interests, Personal, Advisory Role: AstraZeneca, Creatv Microtech; Financial Interests, Personal, Other, Consulting fees: XRAD Therapeutics; Financial Interests, Personal, Research Grant: STCube Pharmaceuticals, Nektar therapeutics, Beyond Spring Pharmaceuticals.
D. Kahangire: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca.
S. Nagar: Financial Interests, Institutional, Funding: AstraZeneca.
M. Ahn: Financial Interests, Personal, Other, Consulting fee: Alpha Pharmaceutical, AstraZeneca, Ono Pharmaceutical Co., Ltd., Roche; Financial Interests, Personal, Other, Consulting fees: Bristol-Myers Squibb, Merck Sharp & Dohme, Takeda; Financial Interests, Personal, Other: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Ono Pharmaceutical Co., Ltd., Roche.
J. Agulnik: Financial Interests, Personal, Other, Consulting fee: AbbVie, Amgen, Bayer, Bristol-Myers Squibb, EMD-Sereno, Exactis, Eli Lilly, Merck, Novartis, Pfizer, Purdue, Roche, Takeda; Financial Interests, Personal, Other, Consulting fees: AstraZeneca.
J. Shih: Financial Interests, Personal, Other, Honoraria: ACTgenomics, Amgen, Genconn Biotech, AstraZeneca, Roche, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Chugai Pharmaceutical, Co., Ltd., Takeda, CStone Pharmaceuticals, Janssen, TTY Biopharm, Orient EuroPharma, MundiPharma, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Roche.
M.J. Hochmair: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Merck Sharp & Dohme, Roche, Takeda; Financial Interests, Personal, Other, Speaker fee: Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Merck Sharp & Dohme, Roche, Takeda.
A. Tufman: Financial Interests, Personal, Full or part-time Employment: LMU University Hospital of Munich; Financial Interests, Personal, Other, Honoraria: Eli Lilly, Pfizer, Novartis, AstraZeneca, Amgen, Celgene, Takeda, Janssen, Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, Boehringer Ingelheim.
J. Chow: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Bristol-Myers Squibb; Financial Interests, Personal, Other, Conference fees: Takeda.
M. Jimenez: Financial Interests, Institutional, Funding: AstraZeneca.
K. Davis: Financial Interests, Institutional, Funding: AstraZeneca.
M. Sandelin: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca.
R. Veluswamy: Financial Interests, Personal, Full or part-time Employment: Icahn School of Medicine at Mount Siani; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb, AstraZeneca, Merck, Boehringer Ingelheim, Merus, Novocure, Regeneron; Financial Interests, Personal, Funding: Bristol-Myers Squibb, Onconova, AstraZeneca, Boehringer Ingelheim.
All other authors have declared no conflicts of interest.
92P - Predictors, surrogate and patient-reported outcomes in neoadjuvant immunotherapy for lung cancer: A single center retrospective study
- L. Bertolaccini (Milan, Italy)
- L. Bertolaccini (Milan, Italy)
- S. Mohamed (Milan, Italy)
- D. Galetta (Milan, Italy)
- F. Petrella (Milan, Italy)
- M. Casiraghi (Milan, Italy)
- C. Diotti (Milan, Italy)
- A. Mazzella (Milan, Italy)
- G. Lo Iacono (Milan, Italy)
- L. Girelli (Milan, Italy)
- G. Sedda (Milan, Italy)
- F. De Marinis (Milan, Italy)
- L. Spaggiari (Milan, Italy)
Abstract
Background
Development of immunotherapy/molecular targeted therapy has significantly increased survival/QoL in advanced stages NSCLC. Aim: to analyze outcome predictors, surrogate outcomes, and PROMs after neoadjuvant immunotherapy for initially unresectable NSCLC.
Methods
Initially unresectable NSCLC (2014–2021) who received immunotherapy ± platinum-based chemo and/or radiotherapy evaluated after response (reduction of primary tumor and/or mediastinal lymphadenopathy/control of distant metastatic disease underwent surgical resection). PROMs were recorded using EORTC QLQ-29.
Results
19 underwent salvage surgery after ICI. 14 had partial response (73.6%), 5 stable diseases. Diagnosis was achieved by EBUS in 8 (42.1%), FNAB in 7 (36.8%), metastasis biopsy in 4 (21.0%). 11 (57.9%) were treated with neoadjuvant platinum-based chemo before or with ICI, 1 (5.2%) pemetrexed before ICI, 5 (26.3%) radiotherapy for metastatic control. 3 (15.7%) had ICI adverse effects. Radiotherapy was never used preoperatively for pulmonary/mediastinal disease. 7 (36.8%) received adjuvant therapy (5 [26.3%] pembrolizumab, 1 [5.2%] pemetrexed, 1 [5.2%] pemetrexed + pembrolizumab). 4 (21.0%) had local relapse (no systemic relapse). Median OS was 19 months (range: 2–57.4). At 2 months, 94.7% were alive (6 months: 89.5%; 31 months: 79.5%). 2 (10.5%) had local recurrence. 2 (10.5%) died due to recurrence, 1 (5.2%) to COVID. 4 (21.0%) relapsed (median DFS: 5.3 months [range: 2.2–13.0]). PROMs were reviewed retrospectively at 30 days/1 year with significant decrease in coughing, side effects of treatment, surgery-related problems.
| Age | 66 (47–76) | ||
|---|---|---|---|
| M/F | 8.5 | ||
| Adenocarcinoma | 11 (57.9) | ||
| Clinical Stage | Before ICI | After ICI | |
| Pembrolizumab | 14 (73.6) | ||
| Lobectomy Pneumonectomy Other | 15 (78.9) | ||
| Pathological response Complete Major | 7 (36.8) | ||
| Coughing | 18.8 ± 15.5 | 5.5 ± 10.2 | 0.19 |
| Shortness of breath | 11.1 ± 11.8 | 8.1 ± 9.8 | 0.84 |
| Side effects of treatment | 10.5 ± 6.5 | 7.7 ± 4.4 | 0.91 |
| Fear of progression | 13.3 ± 16.9 | 6.6 ± 13.8 | 0.40 |
| Surgery related problems | 10.2 ± 9.4 | 4.0 ± 6.0 | 0.53 |
Conclusions
Radical surgical resections following definitive immunotherapy/immune-chemotherapy in selected initially unresectable NSCLC are feasible and safe (low surgical-related mortality and morbidity). Symptoms and surgery-related outcomes were lower with higher QoL due to a selected group of highly motivated patients.
Legal entity responsible for the study
The authors.
Funding
Ministero della Salute.
Disclosure
All authors have declared no conflicts of interest.
93P - A phase II study of camrelizumab plus chemotherapy in patients with medically inoperable early-stage non-small cell lung cancer
- C. Wang (Tianjin, China)
- C. Wang (Tianjin, China)
- Y. Li (Tianjin, China)
- Z. Zhang (Tianjin, China)
- D. Yue (Tianjin, China)
- L. Zhang (Tianjin, China)
Abstract
Background
For medically inoperable patients (pts) with early-stage non-small-cell lung cancer (NSCLC), stereotactic body radiation therapy is recommended, but long-term outcomes are not satisfactory for this population. At present, chemoimmunotherapy has become the standard of care for untreated advanced NSCLC; however, its benefit in medically inoperable early-stage NSCLC is unclear. Herein, we explored the efficacy and safety of camrelizumab (an anti-PD-1 antibody) plus chemotherapy in pts with medically inoperable stage I–IIA NSCLC.
Methods
In this single-arm, single-center, phase II study, treatment-naïve pts with pathologically confirmed medically inoperable stage I–IIA NSCLC and an ECOG PS of 0 or 1 received camrelizumab (200 mg) plus chemotherapy (pemetrexed [500 mg/m2] for non-squamous NSCLC or nab-paclitaxel [260 mg/m2] for squamous NSCLC) intravenously on day 1 of a 21-day cycle. After 4–6 cycles, pts received up to 1 year of camrelizumab (200 mg, day 1, every 21 days) monotherapy as maintenance treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) as per RECIST 1.1, disease control rate (DCR), overall survival (OS), PFS and OS rates at 1, 2 and 5 years, and safety.
Results
From October 19, 2020 to July 4, 2022, 18 pts were enrolled. The median age was 75 years (IQR 71–78). Ten pts (55.6%) were male and 11 pts (61.1%) had adenocarcinoma. As of December 15, 2022, the median PFS was not reached (95% CI 11.1-not reached). Of the 18 pts, six pts (33.3%) achieved partial response, 11 pts (61.1%) had stable disease and one pt (5.6%) was not evaluable. The ORR and DCR were 33.3% (95% CI 13.3%-59.0%) and 94.4% (95% CI 72.7%-99.9%), respectively. The median treatment cycle of camrelizumab was 17 (IQR 11–17). Treatment-related adverse events (TRAEs) occurred in 14 pts (77.8%). Four pts (22.2%) had grade 3 TRAEs, with one each of anemia, platelet count decreased, white blood cell count decreased, and pneumonia. No grade 4 or 5 TRAEs were reported.
Conclusions
Camrelizumab plus single-agent chemotherapy showed promising activity with a manageable safety profile in pts with medically inoperable stage I-IIA NSCLC.
Clinical trial identification
NCT04530227.
Legal entity responsible for the study
C. Wang.
Funding
Jiangsu Hengrui Pharmaceuticals Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.
94P - Neoadjuvant tislelizumab combined with (nab)-paclitaxel plus platinum-based chemotherapy for patients with stage IIA–IIIB squamous NSCLC: A real-world retrospective study
- X. Huang (Hangzhou, China)
- X. Huang (Hangzhou, China)
- Z. Mao (Shanghai, China)
- B. Li (Hangzhou, China)
- M. Hu (Hangzhou, China)
- P. Wang (Hangzhou, China)
- L. Ding (Hangzhou, China)
Abstract
Background
Immunotherapy combined with chemotherapy as neoadjuvant therapy has shown promising efficacy. Tislelizumab is an anti-PD-1 mAb approved in China for the treatment of first-line advanced squamous NSCLC in combination with chemotherapy. This study aimed to evaluate the efficacy of tislelizumab combined chemotherapy as neoadjuvant therapy in resectable stage IIA–IIIB squamous NSCLC in a real-world setting.
Methods
A retrospective analysis included patients (pts) with resectable IIA–IIIB (AJCC 8th) squamous NSCLC who received neoadjuvant tislelizumab combined with chemotherapy at Second Affiliated Hospital of Medical School of Zhejiang University between Apr 2020 and Oct 2022. The primary endpoints were major pathological response (MPR) rate and pathological complete response (PCR) rate; secondary endpoints included objective response rate (ORR) by RECIST1.1, down-staging rate and safety outcomes.
Results
60 pts were included with a median age of 55 (range 41–85) years, and 98% males. 56 pts were administrated with tislelizumab combined with nab-paclitaxel plus platinum-based chemotherapy, and other 4 pts chemotherapy regime was paclitaxel instead of nab-paclitaxel. All pts received 2–3 cycles neoadjuvant therapy. The MPR rate and PCR rate were 81.67%(95%CI:69.56,90.48) and 41.67%(95%CI:29.07,55.12) respectively. The ORR, and down-staging rate were 75%(95%CI:62.14,85.28), 38.3%(95%CI:26.07,51.79), As of 1 Oct 2022, the median follow-up time was 20 (range: 4–29) months, 7 pts experienced recurrence, and 5 of them are non-MPR. For the safety information, mild immune-related AEs such as rash and pneumonitis were experienced in this retrospective analysis.
Conclusions
This real-world retrospective study revealed that tislelizumab combined with (nab)-Paclitaxel and platinum-based chemotherapy is a promising option as neoadjuvant therapy for resectable stage IIA-IIIB squamous NSCLC.
Legal entity responsible for the study
The authors.
Funding
BeiGene (Beijing) Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.
95P - Neoadjuvant treatment pattern and association between real-world event-free survival (rwEFS) and overall survival (OS) in patients (pts) with resected early-stage non-small cell lung cancer (eNSCLC)
- J. Donington (Chicago, United States of America)
- J. Donington (Chicago, United States of America)
- X. Hu (Rahway, United States of America)
- S. Zhang (Boston, United States of America)
- Y. Song (Boston, United States of America)
- C. Gao (Boston, United States of America)
- A. Arunachalam (Rahway, United States of America)
- D. R. Chirovsky (Rahway, United States of America)
- A. Lerner (Boston, United States of America)
- A. Jiang (Boston, United States of America)
- J. Signorovitch (Boston, United States of America)
- A. Samkari (Rahway, United States of America)
Abstract
Background
This study aimed to describe neoadjuvant treatment patterns, rwEFS, OS and assess association between rwEFS and OS in resected eNSCLC.
Methods
This retrospective study used the US SEER-Medicare data (2007–2019) to select pts with newly diagnosed, resected, stage II-IIIB (N2) NSCLC (AJCC 8th edition) treated with neoadjuvant therapy. Index date was defined as neoadjuvant therapy initiation. rwEFS (time from index date to first recurrence or death, whichever first) and OS (time from index date to death) were described using Kaplan-Meier analysis and correlation was assessed using normal scores rank test. OS was compared between pts with and without recurrence by 1, 2, and 3-year landmarks after index date; hazard ratios were estimated using Cox models adjusted for key baseline factors.
Results
221 pts (156 with recurrence and 65 without) met eligibility criteria (median follow-up: 32.7 months). Selected pt characteristics are presented in the table. ∼97% received platinum-based neoadjuvant therapy and ∼49% received neoadjuvant chemoradiation. Carboplatin + paclitaxel, cisplatin + etoposide, and carboplatin + pemetrexed are most frequently used regimens. Median rwEFS was 17.6 months; median OS was 48.5 months. The normal scores rank correlation demonstrated a statistically significant correlation between rwEFS and OS (0.68; P < 0.001). Pts with recurrence by each landmark had significantly shorter OS than those without recurrence (All Ps <0.01). Adjusted Cox models indicated that pts with recurrence had 2.7–3.2 times increased risk of death (All Ps <0.05).
| Patient characteristics | |
|---|---|
| Age at surgery (years), mean ± SD | 72.1 ± 4.9 |
| Male, N (%) | 126 (57.0%) |
| White | 191 (86.4%) |
| Adjuvant chemotherapy, N (%) | 67 (30.3%) |
| Post-operative radiotherapy, N (%) | 56 (25.3%) |
| rwEFS rate | |
| 1-year | 61.1% |
| 2-year | 42.4% |
| 3-year | 33.3% |
| 4-year | 26.9% |
| 5-year | 20.9% |
| OS rate | |
| 1-year | 91.4% |
| 2-year | 72.4% |
| 3-year | 60.6% |
| 4-year | 50.3% |
| 5-year | 44.9% |
Abbreviations: NSCLC: non-small cell lung cancer; rwEFS: real-world event-free survival; OS: overall survival; SD: standard deviation.
Conclusions
Among pts with resected eNSCLC receiving neoadjuvant therapy, poor survival outcomes were observed. rwEFS is positively and significantly associated with OS. These findings highlight the need for and importance of more effective treatments for this pt population.
Legal entity responsible for the study
The authors.
Funding
Merck and Co. Inc.
Disclosure
J. Donington: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck and Co. Inc, Bristol-Myers Squibb, Roche/Genentech; Financial Interests, Personal, Advisory Board: AstraZeneca, Merck and Co. Inc, Bristol-Myers Squibb, Roche/Genentech.
X. Hu: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc; Financial Interests, Personal, Stocks/Shares: Merck and Co. Inc.
S. Zhang: Financial Interests, Institutional, Other, Su Zhang is an employee of Analysis Group Inc., which received research funding from Merck and Co., Inc. to conduct this study: Merck and Co.
Y. Song: Financial Interests, Institutional, Other, Yan Song is an employee of Analysis Group Inc., which received research funding from Merck and Co., Inc. to conduct this study: Merck and Co. Inc.
C. Gao: Financial Interests, Institutional, Other, Chi Gao is an employee of Analysis Group Inc., which received research funding from Merck and Co., Inc. to conduct this study: Merck and Co. Inc.
A. Arunachalam: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc; Financial Interests, Personal, Stocks/Shares: Merck and Co. Inc.
D. Chirovsky: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc; Financial Interests, Personal, Stocks/Shares: Merck and Co. Inc.
A. Lerner: Financial Interests, Institutional, Other, Ari is an employee of Analysis Group Inc., which received research funding from Merck and Co., Inc. to conduct this study: Merck and Co. Inc.
A. Jiang: Financial Interests, Institutional, Other, Anya is an employee of Analysis Group Inc., which received research funding from Merck and Co., Inc. to conduct this study: Merck and Co. Inc.
J. Signorovitch: Financial Interests, Institutional, Other, James Signorovitch is an employee of Analysis Group Inc., which received research funding from Merck and Co., Inc. to conduct this study: Merck and Co. Inc.
A. Samkari: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc; Financial Interests, Personal, Stocks/Shares: Merck and Co. Inc.
96P - Characteristics of patients with resectable non-metastatic non-small cell lung cancer treated with or without neoadjuvant therapy in Europe and Canada: A real-world survey
- H. BAILEY (Bollington, United Kingdom)
- H. BAILEY (Bollington, United Kingdom)
- S. Lucherini (Uxbridge, United Kingdom)
- H. Burlison (BOLLINGTON, United Kingdom)
- P. Lam (Lawrenceville, United States of America)
- L. Vo (Lawrenceville, United States of America)
- N. Varol (Uxbridge, United Kingdom)
Abstract
Background
There are limited data on real world usage of neoadjuvant (neo) treatment (tx) in clinical practice in non-metastatic non-small cell lung cancer (nmNSCLC). As immunotherapies (IO) emerge in the resectable setting, we aimed to describe characteristics and tx patterns of patients (pts) receiving neo tx for resectable nmNSCLC.
Methods
Data were drawn from the Adelphi nmNSCLC Disease Specific Programme™, a point in time survey of 274 oncologists/pulmonologists/surgeons in France (FR), Germany (DE), Italy (IT), Spain (ES), United Kingdom (UK) and Canada (CA) between Apr-Nov 2022. Physicians provided information on their next four consulting pts with resectable nmNSCLC [random] (n = 1074) and an additional four pts receiving/received any neo and/or adjuvant tx [oversample] (n = 1090).
Results
Of 1074 random pts, 208 (19.4%) received neo tx; country splits were 45/203 (22.2%) FR, 36/200 (18.0%) DE, 39/205 (19.0%) IT, 49/200 (24.5%) ES, 30/198 (15.2%) UK and 9/68 (13.2%) CA. Characteristics of pts who did and did not receive neo tx [random and oversample] are shown in the table. Of 739 neo pts, cisplatin + vinorelbine (18.8%), carboplatin + paclitaxel (11.0%) and cisplatin + gemcitabine (9.6%) were the most common txs initially received. Radiotherapy was administered to 22.2% alongside or subsequent to neo tx. Pathological response for pts who concluded neo tx (n = 251) was complete in 12.0%, major in 43.8%, and neither complete nor major in 22.7%. Top three reasons for prescribing neo tx were to; improve overall survival (OS) (64.1%), facilitate surgery of resectable pts (60.5%) and improve event-free survival (42.8%).
| Received neo tx (n = 739) | Received surgery without neo tx (n = 1425) | |
|---|---|---|
| Age (mean, years) | 63.2 | 64.9 |
| Male, % | 65.2 | 64.1 |
| Stage at dx | ||
| 0–IIB | 28.8 | 77.9 |
| IIIA–C | 66.6 | 16.0 |
| Unknown | 4.6 | 6.1 |
| Histology, % | ||
| Squamous cell | 37.8 | 37.2 |
| Adenocarcinoma | 55.9 | 58.2 |
| Large cell carcinoma | 5.0 | 3.6 |
| Other | 0.8 | 0.5 |
| Unknown | 0.5 | 0.4 |
| ECOG PS at dx, % | ||
| 0–1 | 93.4 | 93.2 |
| 2+ | 6.0 | 6.0 |
| Unknown | 0.7 | 0.8 |
| Biomarker testing, % | ||
| PD-L1 | 62.1 | 62.9 |
| Driver mutations | 58.9 | 60.4 |
| PD-L1 expression, % | n = 450 | n = 872 |
| <1% | 28.7 | 31.3 |
| 1–49% | 58.2 | 54.9 |
| ≥50% | 13.1 | 13.8 |
| Driver mutations | n = 435 | n = 861 |
| Yes (some/all results) | 79.3 | 76.9 |
8th TNM edition
EGFR, ALK, ROS1, RET, BRAF, MET, KRAS dx, diagnosis; tx, treatment; ECOG, Eastern Cooperative Oncology Group
Conclusions
Neo tx was prescribed to one third of nmNSCLC pts, two thirds of whom were stage IIIA–C at diagnosis. Prescribing neo tx aimed to improve OS and facilitate surgery of resectable pts. With recent advances in neo IO tx showing benefits over chemotherapy, neo tx may be a realistic option for more pts.
Legal entity responsible for the study
Adelphi Real World.
Funding
Has not received any funding.
Disclosure
H. Bailey: Financial Interests, Institutional, Full or part-time Employment: Adelphi Real World.
S. Lucherini: Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Non-Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb.
H. Burlison: Financial Interests, Institutional, Full or part-time Employment: Adelphi Real World.
P. Lam: Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Non-Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb.
L. Vo: Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Non-Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb.
N. Varol: Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Non-Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb.
97P - Aumolertinib as adjuvant therapy in postoperative EGFR-mutated stage I–III non-small cell lung cancer with high-risk pathological factors
- X. Chen (Ningbo, China)
- X. Chen (Ningbo, China)
- J. He (Ningbo, China)
- H. Shen (Ningbo, China)
- Y. Xi (Ningbo, China)
- B. Chen (Ningbo, China)
- X. He (Ningbo, China)
- J. Gao (Ningbo, China)
- H. Yu (Ningbo, China)
- W. Shen (Ningbo, China)
Abstract
Background
Pulmonary adenocarcinoma with high-risk pathological factors are known to be associated with poor prognosis in early-stage non-small-cell lung cancer (NSCLC). Aumolertinib is a third-generation EGFR-TKI that has efficacy in EGFR sensitive and resistant NSCLC. The efficacy of aumolertinib as adjuvant therapy in resected stage I–III NSCLC with high-risk pathological factors remains unknown.
Methods
Patients underwent completely resected pathologic stage I–III lung adenocarcinoma with micropapillary/solid component with or without complex glands were enrolled. Patients were assigned to aumolertinib group (group A): patients with EGFR mutation-positive (exon 19 deletion or L858R) received aumolertinib (110 mg daily), group B (EGFR mutation positive) and group C (EGFR mutation negative or unknown). Both group B and C received observation for disease recurrence and no adjuvant therapy was given. The primary endpoint was investigator assessed disease-free survival (DFS) and safety was evaluated.
Results
A total of 115 stage I–III lung adenocarcinoma with micropapillary or solid component patients were enrolled. 70 patients were EGFR mutation-positive (45 in aumolertinib group, 25 in group B). 45 patients were EGFR mutation-negative or unknown and assigned to group C. At data cut-off, all patients in aumolertinib group have no symptoms of tumor recurrence and continued aumolertinib, the 1-year DFS was 100%. In group B, 64% patients were alive and disease-free, 3 of 25 patients had tumor recurrence within 1 year (1-year DFS: 88%). In group C, 89% patients were alive and disease-free, 1-year DFS was 93%. Compared two no EGFR-TKI treatment groups, the recurrent ratio in EGFR mutated patients was higher than EGFR negative or unknown group. There were no grade ≥3 adverse events occurred during aumolertinib treatment, rash (15%), pruritus (27%), diarrhea (11%) and mouth ulceration (11%) were common adverse events.
Conclusions
This is the first report that aumolertinib has efficacy in patients with completely resected stage I-III EGFR mutated NSCLC with high-risk pathological factors. EGFR mutation positive as a poor prognosis factor was associated with higher recurrence than the negative or unknown.
Editorial acknowledgement
Medical writing support was provided by Hang Zhang, of Hansoh Pharma, Shanghai, China.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
98P - Adjuvant aumolertinib in resected EGFR-mutated non-small cell lung cancer: A multiple-center real-world experience
- Q. Zhang (Hangzhou, China)
- Q. Zhang (Hangzhou, China)
- L. Ke (Hangzhou, China)
- S. Huang (Hangzhou, China)
- Y. Yang (Hangzhou, China)
- T. He (Hangzhou, China)
- H. Sun (Taizhou, China)
- Z. Wu (Hangzhou, China)
- X. Zhang (Wenzhou, China)
- H. Zhang (Shanghai, China)
- W. Lv (Hangzhou, China)
- J. Hu (Hangzhou, China)
Abstract
Background
Aumolertinib as a novel third-generation Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI) has been shown to be efficacy in EGFR mutations and also in CNS metastasis NSCLC. We aimed to evaluate long-term efficacy and safety of adjuvant aumolertinib in postoperative patients.
Methods
A total of 215 patients who underwent radical lung cancer surgery with EGFR-sensitizing mutations from four different medical centers were enrolled and received aumolertinib 110 mg daily, the medication time (6months-36months) depended on the pathological stage and physical conditions. The disease-free survival (DFS), safety and tolerability were evaluated.
Results
The study retrospectively analyzed 215 patients with pathologically confirmed adenocarcinoma, EGFR mutation-positive, stage Ia2–Ⅲa NSCLC (132 females, 87 males, ranging in age from 27 to 86 years, with a median age of 63). All patients were followed for at least 6 months, 40 patients have been followed up for over 2 years, and 110 patients have been followed for over 1 year. At data cutoff, all patients were alive, only one patient had bone metastasis, and no patient presented with CNS metastasis. 2-year DFS was 99%. During aumolertinib treatment, 69 patients (69/215, 32.1%) experienced drug-related adverse reactions. Rash (39/215, 18.1%), diarrhea (15/215, 7.0%), abnormal liver and kidney function (12/215, 5.6%), and mouse ulcer (11/215, 5.1%). There was no grade ≥3 adverse events that occurred, and no patients withdrew from treatment due to adverse reactions.
Conclusions
Based on our previous study, we expanded the number of patients and extended the follow-up period. Our study further demonstrates the pronounced efficacy of aumolertinib in the postoperative adjuvant treatment of NSCLC with an excellent safety profile. Long term follow-up of our study is ongoing to investigate further survival outcomes.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Zhang: Financial Interests, Personal, Sponsor/Funding: Hansoh Pharma.
All other authors have declared no conflicts of interest.
99P - The optimal treatment for patients with stage I non-small cell lung cancer: Minimally invasive lobectomy or stereotactic ablative radiotherapy?
- J. De Ruiter (Amsterdam, Netherlands)
- J. De Ruiter (Amsterdam, Netherlands)
- V. Van der Noort (Amsterdam, Netherlands)
- J. Van Diessen (Amsterdam, Netherlands)
- E. F. Smit (Amsterdam, Netherlands)
- R. Damhuis (Utrecht, Netherlands)
- K. Hartemink (Amsterdam, Netherlands)
Abstract
Background
The standard treatment for operable patients with stage I non-small cell lung cancer (NSCLC) is a minimally invasive lobectomy (MIL). However, stereotactic ablative radiotherapy (SABR) is increasingly being used. The ESLUNG study compares the outcome of MIL and SABR in operable patients.
Methods
In this retrospective cohort study with 38 participating centres, patients with clinical stage I NSCLC (TNM7), treated in 2014–2016 with MIL or SABR, were included. Recurrence rates 5-year recurrence-free survival (RFS), overall survival (OS) and lung-cancer-specific mortality (LCSM) were calculated. RFS and OS were compared after adjusting for confounding by propensity score (PS) weighting.
Results
In total, 2183 patients (1211 MIL and 972 SABR) were included. SABR patients were significantly older, had more comorbidities and poorer lung function and performance status. Postoperative nodal upstaging occurred in 12.1% of operated patients. 30-day mortality was 1.0% after MIL and 0.2% after SABR. SABR patients developed significantly more regional recurrences (18.1 versus 14.2%) and/or distant metastases (26.2 versus 20.2%) with a similar local recurrence rate (13.1 versus 12.1%). Unadjusted 5-year RFS and OS were 58.0 versus 25.1% and 70.2 versus 40.3% after MIL and SABR, respectively. 5-year LCSM was 17.4% after MIL and 24.0% after SABR (HR 0.74, 95% CI 0.61–0.90). PS-weighted analyses showed – in patients considered operable – better RFS after MIL (HR 0.70, 95% CI 0.49–0.99), but no significant difference in OS (HR 0.80, 95% CI 0.53–1.21).
Conclusions
In operable patients with stage I NSCLC, MIL leads to fewer regional recurrences and distant metastases than SABR. However, OS did not differ significantly. Future studies should focus on optimization of patient selection for MIL or SABR to further reduce postoperative mortality after MIL and nodal failures after SABR.
Legal entity responsible for the study
K.J. Hartemink.
Funding
Dutch Cancer Society (KWF Kankerbestrijding).
Disclosure
All authors have declared no conflicts of interest.
100P - Effects of U.S. insurance type on 5-year all-cause mortality after robotic-assisted pulmonary lobectomy for lung cancer
- A. O. Dumitriu Carcoana (Tampa, United States of America)
- A. O. Dumitriu Carcoana (Tampa, United States of America)
- J. Singh (Tampa, United States of America)
- J. A. Malavet (Tampa, United States of America)
- J. C. Marek (Tampa, United States of America)
- K. M. Labib (Tampa, United States of America)
- W. N. Doyle Jr (Tampa, United States of America)
- W. J. West III (Tampa, United States of America)
- P. Deol (Tampa, United States of America)
- C. C. Moodie (Tampa, United States of America)
- J. R. Garrett (Tampa, United States of America)
- J. J. Baldonado (Tampa, United States of America)
- J. R. Tew (Tampa, United States of America)
- J. P. Fontaine (Tampa, United States of America)
- E. Toloza (Tampa, United States of America)
Abstract
Background
Public insurance type has been correlated with worse overall survival in several cohorts of cancer patients in the United States, but few analyses included combination insurance as a discreet insurance category. The objective of this study is to determine whether public, private, or combination insurance type predicted 5-year mortality after robotic-assisted pulmonary lobectomy (RAPL) for lung cancer.
Methods
We retrospectively analyzed 711 patients who underwent RAPL from September 2010 to March 2022 by one surgeon.
Results
Among our 711 study patients, 367 (52%) patients had combination insurance, 144 (20%) had public insurance, and 200 (28%) patients had private insurance. There were no differences in sex, race, body mass index, or tumor characteristics including stage, grade, pathology, histology, size and nodal status. Patients with combination insurance had a higher mean age (p < 0.0001), the largest proportion of former smokers (p = 0.0003), higher Charlson comorbidity index scores (p = 0.0014), more comorbid conditions, and the least estimated blood loss during surgery (p = 0.003). There were no differences in hospital length of stay, discharge disposition, and in-hospital or 30-day mortality. Multivariable regression analysis identified combination insurance type as an independent predictor of 5-year all-cause mortality (hazard ratio, 1.72; 95% CI, 1.08–2.75; p = 0.02;
| Variable | Hazard Ratio (95% CI) | p = value |
|---|---|---|
| Combination Insurance | 1.72 (1.08–2.75) | 0.02 |
| Public Insurance | 1.18 (0.72–1.93) | 0.51 |
| Former Smoker | 0.75 (0.45–1.24) | 0.26 |
| Never Smoker | 0.69 (0.38–1.23) | 0.21 |
| Charlson Comorbidity Index Score | 0.97 (0.76–1.23) | 0.81 |
| Preoperative Chronic Kidney Disease | 4.81 (0.60–38.4) | 0.14 |
| Preoperative Atrial Fibrillation | 1.17 (0.39–3.50) | 0.79 |
| Preoperative Hypertension | 0.95 (0.62–1.46) | 0.82 |
| Preoperative Hyperlipidemia | 1.36 (0.87–2.12) | 0.17 |
| Intraoperatie Estimated Blood Loss | 1.00 (1.00–1.00) | 0.99 |
Conclusions
Although previous studies identified public health insurance as a predictor of worse 5-year overall survival in the United States, in our present cohort, combination insurance type was associated with the greatest risk for all-cause mortality.
Legal entity responsible for the study
The authors.
Funding
University of South Florida Health Morsani College of Medicine.
Disclosure
J.P. Fontaine: Financial Interests, Personal, Training: Intuitive Surgical Corp.
E. Toloza: Financial Interests, Personal, Training: Intuitive Surgical Corp.
All other authors have declared no conflicts of interest.
101P - Evidence base for exercise prehabilitation suggests favourable outcomes for patients undergoing surgery for non-small cell lung cancer despite being of low therapeutic quality: A systematic review and meta-analysis
- M. Voorn (Venlo, Netherlands)
- M. Voorn (Venlo, Netherlands)
- V. E. Van Kampen-van den Boogaart (Venlo, Netherlands)
- G. Bootsma (Heerlen, Netherlands)
- B. Bongers (Maastricht, Netherlands)
- R. Franssen (Venlo, Netherlands)
- T. Hoogeboom (Nijmegen, Netherlands)
Abstract
Background
The aim of this systematic review was to evaluate whether exercise prehabilitation programs reduce postoperative complications, postoperative mortality, and length of hospital stay (LoS) in patients undergoing surgery for non-small cell lung cancer (NSCLC), thereby accounting for the quality of the physical exercise program.
Methods
Two reviewers independently selected randomized controlled trials (RCTs) and observational studies and assessed them for methodological quality and therapeutic quality of the exercise prehabilitation program (i-CONTENT tool). Eligible studies included patients with NSCLC performing exercise prehabilitation and reported the occurrence of 90-day postoperative complications, postoperative mortality, and LoS. Meta-analyses were performed and the certainty of the evidence was graded (Grading of Recommendations Assessment, Development and Evaluation (GRADE)) for each outcome.
Results
Sixteen studies, comprising 2,096 patients, were included. Pooled analyses of RCTs and observational studies showed that prehabilitation reduces postoperative pulmonary complications (OR 0.45), postoperative severe complications (OR 0.51), and LoS (mean difference −2.46 days), but not postoperative mortality (OR 1.11). The certainty of evidence was very low to moderate for all outcomes. Risk of ineffectiveness of the prehabilitation program was high in half of the studies due to an inadequate reporting of the dosage of the exercise program, inadequate type and timing of the outcome assessment, and low adherence.
Conclusions
Although risk of ineffectiveness was high for half of the prehabilitation programs and certainty of evidence was very low to moderate, prehabilitation seems to result in a reduction of postoperative pulmonary and severe complications, as well as LoS in patients undergoing surgery for NSCLC.
Legal entity responsible for the study
M. Voorn.
Funding
Research and Innovation Fund VieCuri (Fonds Wetenschap en Innovatie VieCuri, Venlo, the Netherlands).
Disclosure
All authors have declared no conflicts of interest.
102P - A qualitative stakeholder analysis of beliefs, facilitators, and barriers for a feasible prehabilitation program before lung cancer surgery
- M. Voorn (Venlo, Netherlands)
- M. Voorn (Venlo, Netherlands)
- M. Janssen-Heijnen (Venlo, Netherlands)
- B. Bongers (Maastricht, Netherlands)
- C. Schröder (Utrecht, Netherlands)
- V. E. Van Kampen-van den Boogaart (Venlo, Netherlands)
- G. Bootsma (Heerlen, Netherlands)
- E. M. Bastiaansen (Bergen op Zoom, Netherlands)
Abstract
Background
In order to develop a feasible prehabilitation program before surgery of NSCLC, this study aimed to gain insight into beliefs, facilitators, and barriers of 1) healthcare professionals to refer patients to a prehabilitation program, 2) patients to participate in and adhere to a prehabilitation program, and 3) informal caregivers to support their loved ones.
Methods
Semi-structured interviews were conducted with healthcare professionals, patients who underwent surgery for NSCLC, and their informal caregivers. The capability, opportunity, and motivation for behavior-model (COM-B) guided the development of the interview questions. Results were analyzed thematically.
Results
The interviews were conducted with twelve healthcare professionals, seventeen patients, and sixteen informal caregivers. Healthcare professionals mentioned that multiple professionals should facilitate the referral of patients to prehabilitation within primary and secondary healthcare involved in prehabilitation, considering the short preoperative period. Patients did not know that a better preoperative physical fitness and nutritional status would make a difference in the risk of postoperative complications. Patients indicated that they want to receive information about the aim and possibilities of prehabilitation. Most patients preferred a group-based physical exercise training program organized in their living context in primary care. Informal caregivers could support their loved one when prehabilitation takes place by doing exercises together.
Conclusions
A prehabilitation program should be started as soon as possible after the diagnosis of lung cancer. Receiving information about the purpose and effects of prehabilitation in a consult with a physician seems crucial to patients and informal caregivers to be involved in prehabilitation. Support of loved ones in the patient's own living context is essential for adherence to a prehabilitation program.
Legal entity responsible for the study
M. Voorn.
Funding
Research and Innovation Fund VieCuri (Fonds Wetenschap en Innovatie VieCuri, Venlo, the Netherlands).
Disclosure
All authors have declared no conflicts of interest.
103P - Patient and clinician perspectives on adjuvant treatment in early-stage non-small cell lung cancer (NSCLC): Qualitative results
- H. Collacott (Bethesda, United States of America)
- H. Collacott (Bethesda, United States of America)
- P. Okhuoya (Northolt, United Kingdom)
- M. Sandelin (Molndal, Sweden)
- C. Michaels-Igbokwe (Bethesda, United States of America)
Abstract
Background
Despite advances in treatment options, little is known about patient and clinician perspectives on the benefits of adjuvant treatment in early-stage NSCLC. Qualitative interviews with patients and clinicians explored concepts related to adjuvant treatment benefit, including the value of prolonging survival.
Methods
Patients with fully resected stage IB-IIIA NSCLC who had or had not received adjuvant treatment and treating oncologists, thoracic surgeons, and pulmonologists in 13 countries completed online interviews. Themes investigated were informed by a review of the literature and clinical data for comparator treatments and included NSCLC symptoms, expectations for adjuvant treatment, and desired outcomes.
Results
Fifty-eight patients (Asia Pacific n = 9, Europe n = 29, North America n = 10, South America n = 10) and 109 clinicians (Asia Pacific n = 30, Europe n = 54, Middle East n = 5, North America n = 10, South America n = 10) completed an interview. Mean patient age was 56 years. Most patients were female (n = 34, 59%) and had received adjuvant treatment for NSCLC (n = 32, 55%). Most clinicians were oncologists (n = 69, 63%) and 20% were female (n = 22). The most common desired treatment benefits related to survival. In the patient sample this included cure or remission (n = 27, 47%), avoiding disease spread (n = 11, 19%), and delaying recurrence (n = 6, 10%), while clinicians reported overall survival (OS) (n = 97, 89%), disease-free survival (DFS) (n = 78, 72%), and progression-free survival (n = 21, 19%). For adjuvant treatment-naïve patients, tolerability was an important treatment consideration (n = 7, 27%). Clinician treatment decisions were influenced by treatment tolerability and quality of life (QoL) concerns (both n = 37, 34%), as well as reduced symptom burden (n = 22, 20%).
Conclusions
Survival outcomes including OS and DFS were most frequently mentioned as desired benefits but were described differently by patients and clinicians. Treatment tolerability and QoL on treatment were also important considerations. Results will be used to inform the design of a quantitative study assessing the trade-offs participants are willing to make between OS, DFS and treatment risk.
Legal entity responsible for the study
Evidera Inc.
Funding
AstraZeneca.
Disclosure
H. Collacott: Financial Interests, Institutional, Full or part-time Employment: Evidera.
P. Okhuoya: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Institutional, Stocks/Shares: AstraZeneca.
M. Sandelin: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Institutional, Stocks/Shares: AstraZeneca.
C. Michaels-Igbokwe: Financial Interests, Institutional, Full or part-time Employment: Evidera; Financial Interests, Institutional, Stocks/Shares: Evidera; Financial Interests, Institutional, Principal Investigator: Evidera.
104TiP - MRD Evaluation of aumolertinib in EGFR mutation-positive stage IB and stage IA2–3 NSCLC after complete surgical resection: A multicenter, open-label, single-arm study (ASSIST)
- C. Cheng (Guangzhou, China)
- C. Cheng (Guangzhou, China)
- J. Zhang (Guangzhou, China)
- X. Ben (Guangzhou, China)
- S. Li (Guangzhou, China)
- D. Wang (Shanwei, China)
- W. Lin (Gaozhou, China)
- W. Lv (Jieyang, China)
Abstract
Background
Surgery is the standard treatment for early non-small cell lung cancer (NSCLC). However, even after complete surgical resection, about 20% of stage I patients (pts) are still exposed to early recurrence or metastasis. Epidermal growth factor receptor (EGFR) mutation is often a poor prognostic factor for early recurrence and metastasis. There are few treatment options for pts with EGFR-mutant stage IB and stage IA2-3 NSCLC, and lack of standard adjuvant therapy currently. Aumolertinib is a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) approved in China to treat EGFR-mutant NSCLC, and application for listing permission has been accepted by European Medicines Agency (EMA). Preliminary studies have shown that minimal residual disease (MRD) detection plays an important role in guiding treatment and predicting disease progression. The ASSIST (ChiCTR2200063184) study is designed to assess the efficacy and safety of aumolertinib as adjuvant therapy in pts with EGFR-mutant stage IB and stage IA2-3 NSCLC according to MRD detection.
Trial design
This multicenter, open-label, single-arm study is ongoing and aims to enroll approximately 130 pts with histologically confirmed stage IB or stage IA2-3 invasive NSCLC after standard radical surgery, harboring sensitive EGFR mutations, aged 18–75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0–1, and have not previously received chemotherapy, radiotherapy or targeted therapy for NSCLC. Eligible pts receive aumolertinib 110 mg orally once daily until disease progression or complete the overall treatment for 3 years. Stratified by the results of two postoperative MRD detections. Pts receive aumolertinib as adjuvant therapy regardless of whether MRD positive or negative. Plasma samples are collected at week 12 and 24 after surgery and every 24 weeks at each follow-up time to evaluate MRD status. The primary endpoint is disease-free survival (DFS) rate at 3 years. Secondary endpoints include DFS rate at 4 and 5 years, overall survival (OS) and safety. The first patient in (FPI) was in July 2022, and the estimated study completion date is Q3 2024.
Clinical trial identification
ChiCTR2200063184 (release date: September 1, 2022).
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
105P - Development and assessment of artificial intelligence detection of lung nodules on chest roentgenograms
- M. Higuchi (Aizuwakamatsu, Japan)
- M. Higuchi (Aizuwakamatsu, Japan)
- T. Nagata (Tokyo, Japan)
- J. Suzuki (Fukushima, Japan)
- T. Yabuki (Aizuwakamatsu, Japan)
- S. Inomata (Aizuwakamatsu, Japan)
- H. Suzuki (Fukushima, Japan)
Abstract
Background
Artificial intelligence (AI) based on deep learning and convolutional neural networks (CNN) has been applied to various medical fields. We have started to develop novel AI to support detection of lung cancer, which will enable physicians to efficiently perform interpretation of radiograms and diagnosis.
Methods
We analyzed the image features as teacher data using 853 chest X-ray images (401 normal images and 452 abnormal images) from Fukushima Preservative Service Association of Health, in which lung cancer screening was mainly conducted and more than 100 000 chest roentgenograms from the NIH database. We categorized these data into two groups, according to including NIH datasets (group A) or not (group B). Then we integrated their datasets for deep learning and CNN using ImageNet to develop proprietary AI algorithm, and analyzed the accuracy of interpretation of radiograms statistically. We also demonstrated the abnormal shadow in the form of heat map display on each chest roentgenogram for easy visualization and also showed positive probability score as an index value (from 0.0 to 1.0), which indicated the possibility of lung cancer. The accuracy of our AI system has been improved by using technology that absorbs differences in radiographic apparatus and imaging environments.
Results
Our novel AI showed the accuracy of 0.74 for AUC, 0.75 for sensitivity and 0.74 for specificity in the group A, and 0.80 for AUC, 0.73 for sensitivity and 0.75 for specificity in the group B. These AI systems used the positive probability cutoff value of 0.5. Both groups are superior to the accuracy of radiologists (AUC 0.71) and also compatible to previous study reports (AUC 0.78). We also demonstrated the heat map display on the monitor screen clearly, if each roentgenogram had abnormal shadows.
Editorial acknowledgement
The authors thank Dr. Karl Embleton, DVM, from Edanz Group for editing a draft of this abstract.
Legal entity responsible for the study
M. Higuchi.
Funding
Grants‐in‐aid for Scientific Research.
Disclosure
All authors have declared no conflicts of interest.
106P - AI negative predictive performance exceeds that of radiologists in volumetric-based risk stratification of lung nodules detected at baseline in a lung cancer screening population
- H. L. Lancaster (Groningen, Netherlands)
- H. L. Lancaster (Groningen, Netherlands)
- M. A. Heuvelmans (Groningen, Netherlands)
- D. Yu (Seoul, Korea, Republic of)
- J. Yi (seoul, Korea, Republic of)
- G. H. De Bock (Groningen, Netherlands)
- M. Oudkerk (Groningen, Netherlands)
Abstract
Background
Lung cancer is the leading cause of cancer-related mortality due to the late stage at which it is diagnosed. When detected at stage 4, 5-year survival is <5%. Whereas lung cancer detected at stage 1, has a 5-year survival >75%. Early detection can be achieved through LDCT lung cancer screening in a high-risk population. Despite being proven effective, widespread implementation remains a challenge for multiple reasons. One of which, the ever-increasing workloads which radiologists face. AI could be crucial in overcoming this challenge.
Methods
Performance of different versions of an AI-prototype (AVIEW LCS; v1.0.34, v1.1.39.14, and v1.1.42.56) was analysed in 283 ultra-LDCT baseline scans. Volumetric nodule measurements from independent reads of the AI-prototypes were compared that of five experienced radiologists, and an independent consensus reference read was performed. Discrepancies between individual reads and consensus were classified as follows; positive misclassifications (nodules classified by the reader/AI as ≥100 mm3, which at the reference consensus read were <100 mm3) and negative misclassifications (nodules classified as a <100 mm3 by the reader/AI, which at consensus read were ≥100 mm3).
Results
Using AVIEW LCS v1.0.34, 1149 nodules were detected of which 878 were classified as solid non-calcified. For v1.1.39.14 and v1.1.42.55, 1502 nodules were detected of which 1019 were solid non-calcified. Overall, v1.0.34 had 61 discrepancies (53 positive and 8 negative misclassifications), and v1.1.39.14 and v1.1.42.56 both had 32 discrepancies (28 positive and 4 negative). The improved AI versions (v1.1.39.14 and v1.1.42.56) had a better negative predictive value than 4 radiologists and equivalent negative predictive value to the 5th radiologist.
Conclusions
AI can surpass the negative predictive performance of experienced radiologists, meaning it could provide a solution to reducing radiologists’ workload associated with lung cancer screening if used as a first read filter.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D. Yu: Other, Personal, Full or part-time Employment: Coreline Soft. J. Yi: Other, Personal, Full or part-time Employment: Coreline Soft. All other authors have declared no conflicts of interest.
107P - Artificial intelligence-based volumetric classification of pulmonary nodules in Chinese baseline lung cancer screening population (NELCIN-B3)
- Y. Mao (Groningen, Netherlands)
- Y. Mao (Groningen, Netherlands)
- H. L. Lancaster (Groningen, Netherlands)
- B. Jiang (Rotterdam, Netherlands)
- D. Han (groningrn, Netherlands)
- M. Vonder (Groningen, Netherlands)
- M. D. Dorrius (Groningen, Netherlands)
- D. Yu (Seoul, Korea, Republic of)
- J. Yi (seoul, Korea, Republic of)
- G. H. De Bock (Groningen, Netherlands)
- M. Oudkerk (groningen, Netherlands)
Abstract
Background
Developments in artificial intelligence (AI) systems to assist radiologists in reading low-dose computed tomography (LDCT) could improve lung cancer screening efficiency by triaging negative screenings. Our aim is to evaluate the performance of an AI system as an independent reader when used to rule-out negative scans (with no nodules/nodules <30 mm3) in LDCT lung cancer baseline screening in a Chinese population.
Methods
362 individuals from the Netherlands and China Big 3 (NELCIN-B3) study with at least one non-calcified solid-component nodule were included. Volumetric nodule measurement was performed on all scans by two experienced radiologists and a fully automated AI lung cancer screening software (AVIEW LCS, v1.1.39.14, Coreline Soft) independently. The largest non-calcified solid-component nodule was determined for each scan. Discrepancies between two radiologists or the AI were reviewed by a consensus panel and stratified into two groups based on NELSON-plus/EUPS protocol threshold: PM was indeterminate/positive nodule (≥100 mm3) classified by radiologists/AI, which at consensus read was negative (<100 mm3); NM was negative result classified by radiologists/AI (<100 mm3), which at consensus read were indeterminate/positive (≥100 mm3).
Results
When looking at the discrepancies for the largest solid-component nodule per participant; 34 (9.4%; 23 PM, 11 NM) discrepancies were reported for AI, compared to 31 (8.6%; 0 PM, 31 NM), and 27 (7.5%; 8 PM, 19 NM) discrepancies for radiologist 1, and 2, respectively. 13 out of 23 PM findings by AI were due to vessel segmentation, 7 were non-nodular morphology, and 3 were incorrect nodule type classification.
Conclusions
In a Chinese baseline lung cancer screening population, the use of an AI system as an independent reader to triage negative scans resulted in the lowest negative-misclassification result compared to radiologists.
Legal entity responsible for the study
The authors.
Funding
Supported by the Royal Netherlands Academy of Arts and Sciences (grant PSA_SA_BD_01). Y.M. supported by the China Scholarship Council (CSC no. 202008440409).
Disclosure
All authors have declared no conflicts of interest.
108P - Optimization of automatic emphysema detection in lung cancer screening dataset
- H. Liu (Groningen, Netherlands)
- H. Liu (Groningen, Netherlands)
- D. Han (groningrn, Netherlands)
- Y. Mao (groningen, Netherlands)
- M. Vonder (groningen, Netherlands)
- M. Heuvelmans (groningen, Netherlands)
- J. Yi (seoul, Korea, Republic of)
- Z. Ye (Tianjin, China)
- H. De Koning (Rotterdam, Netherlands)
- M. Oudkerk (groningen, Netherlands)
Abstract
Background
To improve the detection of early emphysema in a low dose CT (LDCT) lung cancer screening dataset.
Methods
We selected 352 participants from a regional community health center lung cancer screening dataset. Unenhanced low dose CTs were performed using Definition AS (Somatom Definition AS 64), at inspiration, in spiral mode at 120 kVp and 35 mAs. Images were reconstructed with B30f kernel at 2.0/1.0 mm thickness. AI based post-processing software, Aview (Coreline soft, v. 1.0.40), was used to automatically segment the lungs while excluding the pulmonary vessels and bronchus. Emphysema was quantified by voxel counting below a Hounsfield unit (HU) threshold. A wide range of thresholds from −900 to −1024 HU were used. Three readers including one experienced general radiologist (reader A) and two trainees in thoracic radiology (reader B, C) read the CT images by evaluating the emphysema according to the Fleischner criteria. Inter-reader agreement was evaluated using statistical analysis with Cohen's Kappa. Spearman analysis and ROC (Receiver operating characteristic) curve were used to assess the correlation between quantified emphysema under different HU thresholds and reader visual evaluation.
Results
184 (52.3%), 146 (41.5%), and 185 (52.6%) of the cases were classified respectively by reader A, reader B and reader C as positive for emphysema. All readers showed high agreement in diagnosis of the cases. The p value of Spearman analysis is less than 0.05, demonstrating a statistically significant correlation between emphysema volume and the visual classification under different thresholds. The optimal HU threshold was −1000 UH for all readers. The area under the curve (AUC) was 0.799 (95%CI: 0.751–0.847) for reader A, 0.797 (95%CI: 0.751–0.843) for reader B, and 0.785 for reader C (95%CI: 0.738–0.832).
Conclusions
Threshold of −1000 HU was determined to be optimal for the early detection of emphysema in LDCT lung cancer screening dataset. HU threshold optimization for automatic early emphysema detection by CT is indicated.
Legal entity responsible for the study
The authors.
Funding
Supported by the Royal Netherlands Academy of Arts and Sciences (grant PSA_SA_BD_01). Y.M. supported by the China Scholarship Council (CSC no. 202008440409).
Disclosure
All authors have declared no conflicts of interest.
109P - Setting up 4D-CT based image guided radiotherapy (IGRT) for locally advanced lung cancer: Is it safe to reduce PTV margin for dosimetric benefit?
- A. Saha (Kolkata, India)
- A. Saha (Kolkata, India)
- A. Mishra (Kolkata, India)
- S. Manna (Kolkata, India)
- T. Ghosh (Kolkata, India)
- J. Bhattacharya (Kolkata, India)
- S. Goswami (Kolkata, India)
- L. N. Biswas (Kolkata, India)
- S. Mitra (Kolkata, India)
- B. Sarkar (Kolkata, India)
- A. Banik (Kolkata, India)
- S. R. Chowdhury (Kolkata, India)
- S. Biswal (Kolkata, India)
- S. Mandal (Kolkata, India)
- K. George (Kolkata, India)
- P. Soren (Kolkata, India)
- M. Gazi (Kolkata, India)
Abstract
Background
4D-CT based IGRT is currently standard in many developed countries; for radical lung cancer radiotherapy. Here, we aim to assess the volumetric and dosimetric differences of 4D-CT based and Helical free breathing CT (FBCT) based radiotherapy planning for lung cancer patients. We would also evaluate the safety of reduced PTV margin for 4D-CT planning.
Methods
46 patients decided for radical radiotherapy was planned based on 4D-CT based contouring with 7 mm PTV margin (PTV_4D). FBCT based volume was also generated using PTV margin of 1 cm all around and 1.3 cm cranio-caudally (PTV_3D). Patients had two IMRT plans for PTV_3D and PTV_4D; using similar planning parameters. Patients were treated with plans generated on 4D-CT based volumes. The FBCT based plans were extrapolated onto the 4D-CT volume and vice versa. Two plans were compared for PTV, PTV coverage by 95% of prescribed dose and organ at risk (OAR) dose. Dice Similarity Coefficient (DIC) was calculated to examine the overlap between PTV_3D and PTV_4D. Set-up data of 890 fractions were also analysed. We calculated the systematic error (Σ) and random error (δ) in each of the three axes, i.e. x, y, z and PTV margin using van Herk formula. We also calculated the translational vector of each fraction of individual patients.
Results
PTV was significantly low with 4D-CT based planning (mean PTV 509 cc vs 739 cc); so as OAR doses (Mean heart dose 11.6 Gy vs 14.5 Gy, Mean lung dose 13.5 Gy vs 15.5 Gy, and Spinal cord max dose 35.7 Gy vs 37.5 Gy). Mean DIC of PTV_3D and PTV_4D was 0.8 (80%). Our calculated PTV margin was 0.7 cm, 1.1 cm and 0.5 cm in X, Y and Z axis. PTV margin calculated for translational vector was 0.4 cm. Percentage of shifts >5 mm was 8.3%, 31.4% and 1.1% in X, Y and Z axis. Percentage of shifts >7 mm was 3.8%, 17.7% and 0.2% in X, Y and Z axis. Translational vector shift >5 mm and >7 mm was 23.1% and 0.2% respectively.
Conclusions
4D-CT based radiotherapy planning for locally advanced lung cancer with reduced PTV margin of 7 mm, can significantly reduce the PTV, OAR doses. However, while using 7 mm PTV daily imaging should be recommended to ensure PTV coverage particularly Y-axis where shifts more than 7 mm can be higher. Further PTV margin reduction to 5 mm was not found to be safe in our set up.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
110P - Volumetric tumor volume doubling time in lung cancer: A systematic review and meta-analysis
- B. Jiang (Rotterdam, Netherlands)
- B. Jiang (Rotterdam, Netherlands)
- D. Han (groningrn, Netherlands)
- M. Heuvelmans (groningen, Netherlands)
- C. Van der Aalst (Rotterdam, Netherlands)
- H. De Koning (Rotterdam, Netherlands)
- M. Oudkerk (groningen, Netherlands)
Abstract
Background
Tumor growth patterns have important implications for determining screening intervals, making treatment decisions, and predicting prognosis. Our study aimed to characterize tumor volume doubling time (VDT) or growth pattern of primary lung cancer and identify factors associated with rapid and indolent growth patterns.
Results
We have identified 26 studies, including 2275 patients with primary lung cancer (mean age range from 54.6 to 72.0 years), comprising 61.6% men and 38.4% women. For overall lung cancer, median VDT ranged from 139 to 357 days and mean VDT ranged from 151 to 408 days. Pooled overall mean VDT was 213 days (95% CI 171 to 256 days, I2 = 90.0%). In subgroup analyses, pooled mean VDT of adenocarcinoma, adenocarcinoma (subsolid), squamous cell, small cell, and other lung cancer were 241, 731, 136, 71, and 183 days, respectively. Rapid growth accounted for 64.8% of overall lung cancer and 23.7% of adenocarcinoma. The most consistent correlations of rapid tumor growth included nodule solidity, non-adenocarcinoma histology subtype, and invasiveness in adenocarcinoma.
Conclusions
Median VDT in overall lung cancer is always £400 days (range 139 to 357 days) with around two-thirds being rapid; solidity and histology subtypes demonstrate the most consistent correlations.
Legal entity responsible for the study
The authors.
Funding
China Scholarship Council (CSC no. 202008440409).
Disclosure
All authors have declared no conflicts of interest.
111P - Application of radiomics signatures and unidimensional vs volumetric measurement of early tumor growth dynamics (TGD) to predict first-line treatment outcomes in patients with stage IV non-small cell lung cancer (NSCLC)
- L. Schwartz (New York, United States of America)
- L. Schwartz (New York, United States of America)
- K. Aggarwal (Princeton, United States of America)
- D. J. Grootendorst (Princeton, United States of America)
- S. Kotapati (Princeton, United States of America)
- M. Fronheiser (Princeton, United States of America)
- B. Zhao (New York, United States of America)
- C. Coronado-Erdmann (Princeton, United States of America)
- M. Micsinai-Balan (Princeton, United States of America)
- M. Karasarides (Princeton, United States of America)
- A. T. Fojo (New York, United States of America)
- K. Brown (Princeton, United States of America)
Abstract
Background
TGD modeling using sum of longest diameters (SLD) is associated with long-term outcomes in NSCLC. Early changes in radiomics features within the tumor may also correlate with survival outcomes. We retrospectively evaluated 3 methods to assess early treatment outcomes: tumor growth rate (g) by SLD, volumetric measurements, and change in radiomics signatures to predict survival outcomes in NSCLC.
Methods
Patients with stage IV NSCLC in CheckMate 9LA treated with first-line nivolumab+ipilimumab+chemotherapy (NIVO+IPI+CHEMO) or CHEMO alone were included. TGD was modeled using radiologically-assessed SLD from ≤5 target lesions or sum of volumes (SVOL) from all measurable lesions >10 mm at baseline, 6, 12, and/or 18 weeks. Measurements were fitted to the TGD model.1 Overall survival (OS) for each growth quartile was estimated by Kaplan–Meier curves. Changes in radiomic features from all measurable lesions >10 mm were assessed at week 6 and 12.
Results
At week 18, low SVOL- and SLD-derived g values were associated with longer median OS across both treatment arms. SVOL-derived g values were more consistent across timepoints if evaluated at week 12 and 18 than SLD-derived g values. Delta radiomics signatures to predict long-term OS at week 6 (table) and 12 performed better than RECIST 1.1 in the NIVO+IPI+CHEMO arm.
Median OS in groups defined by unidimensional vs volumetric estimates of tumor growth, and by RECIST 1.1 criteria of response vs delta radiomics signature
| Median OS, months | SLD measurements | SVOL measurements | ||
|---|---|---|---|---|
| NIVO+IPI+CHEMO | CHEMO alone | NIVO+IPI+CHEMO | CHEMO alone | |
| g quartile1 | 25.8 | 17.9. | 26.4 | 19.1 |
| g quartile4 | 12.5 | 9.5. | 11.6 | 8.2 |
| Median OS, months | RECIST response (NIVO IPI+CHEMO) | Delta radiomics-derived response (NIVO+IPI+CHEMO) | ||
| At 6 weeks | At 6 weeks | |||
| Progressive disease | 7.1 | 7.4 | ||
| Stable disease | 15.0 | 14.5 | ||
| Partial or complete response | 32.5 | 4 |
Four timepoints, week 18. Patients were grouped according to quartiles of g, with quartile 1 representing the subgroup with slowest g.
Conclusions
SVOL-derived g values correlate with longer OS and are more consistent across timepoints than SLD-derived g values at 18 weeks of treatment. Delta radiomics signatures as early as 6 weeks on-treatment were better than RECIST in identifying patients with NSCLC deriving long-term OS benefit. Both findings can potentially inform early decision making in clinical trials and real-world use.
1. Fojo AT et al. J Clin Oncol. 2022;40(16_suppl):Abst 9063.
Clinical trial identification
NCT03215706.
Editorial acknowledgement
Editorial support was provided by Keri Wellington, PhD, and Isobel Markham of Spark Medica Inc.
Legal entity responsible for the study
Bristol-Myers Squibb.
Funding
Bristol-Myers Squibb.
Disclosure
L. Schwartz: Financial Interests, Personal, Advisory Role: Roche, Novartis; Financial Interests, Personal, Research Grant: Merck, Boehringer Ingelheim. K. Aggarwal: Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb; Financial Interests, Institutional, Full or part-time Employment: Bristol-Myers Squibb. D.J. Grootendorst: Financial Interests, Institutional, Full or part-time Employment: Bristol-Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb. S. Kotapati: Financial Interests, Institutional, Full or part-time Employment: Bristol-Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb. M. Fronheiser: Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb; Financial Interests, Institutional, Full or part-time Employment: Bristol-Myers Squibb. B. Zhao: Financial Interests, Personal, Royalties: Varian Medical Systems; Financial Interests, Institutional, Sponsor/Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: National Cancer Institute. C. Coronado-Erdmann: Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb, Incyte. M. Micsinai-Balan: Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb; Financial Interests, Institutional, Full or part-time Employment: Bristol-Myers Squibb; Financial Interests, Personal, Other: Bristol-Myers Squibb. M. Karasarides: Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb; Financial Interests, Institutional, Full or part-time Employment: Bristol-Myers Squibb. A.T. Fojo: Financial Interests, Personal, Advisory Role: Akita Biomedical; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Institutional, Research Grant: Merck, Ipsen, Pfizer. K. Brown: Financial Interests, Institutional, Full or part-time Employment: Bristol-Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb.
112P - Retrospective analysis of the use of immunohistochemistry for the diagnosis of adenosquamous carcinoma of the lung in a Dutch national cohort
- S. Soekhoe (Rotterdam, Netherlands)
- S. Soekhoe (Rotterdam, Netherlands)
- J. Von der Thüsen (Rotterdam, Netherlands)
- F. Van Kemenade (Rotterdam, Netherlands)
- M. Van der Biezen (Rotterdam, Netherlands)
Abstract
Background
Adenosquamous carcinoma (ASC) is a subtype of NSCLC, which can be diagnosed if the tumor meets three criteria: (1) a combination of an adenocarcinoma and squamous cell carcinoma component, (2) the adenocarcinoma part must constitute at least 10% of the tumor, and (3) the squamous cell carcinoma component also has to cover at least 10%. The goal of this study is to determine to which extent immunohistochemistry (IHC) alone is used to diagnose ASC.
Methods
A query was performed through the Dutch National Pathology Archive. All excerpts with a possible ASC were included. Subsequently the excerpts were categorized. Excerpts were included in the ‘certain’ group if ASC was the working diagnosis. Afterwards, this group was subdivided: (1) only IHC for the diagnosis of ASC and (2) all other methods to diagnose ASC. With this distinction the percentages of patients diagnosed with IHC only can be determined.
Results
The query resulted in 1468 excerpts. After categorization and removing duplicates 651 patients remained in the certain group, 267 patients were diagnosed with ASC based on IHC only.
As seen in the table, the diagnosis of ASC slightly increases over time. This might be explained by the introduction of molecular diagnostics (MD). Over time, the guidelines for the performance of MD for systemic therapy of NSCLC changed from ‘adenocarcinoma only’ to all non-squamous carcinomas. Patients with inconclusive IHC were therefore amenable for MD, possibly leading to an increase in ASC diagnosis. Moreover, IHC-only diagnoses appear to have increased over this time period. This might show that IHC is a useful tool in the primary diagnosis of ASC, particularly with the advent of MD.
Number of patients diagnosed with ASC each year with the method used for diagnosis
| Year | Total number ASC | ASC diagnosed with IHC only |
|---|---|---|
| 2004 | 26 | 2 (7.7) |
| 2005 | 31 | 6 (19.4) |
| 2006 | 22 | 5 (22.7) |
| 2007 | 31 | 8 (25.8) |
| 2008 | 37 | 11 (29.7) |
| 2009 | 35 | 12 (34.3) |
| 2010 | 37 | 14 (37.8). |
| 2011 | 28 | 14 (50.0) |
| 2012 | 38 | 18 (47.4) |
| 2013 | 27 | 13 (48.1) |
| 2014 | 36 | 19 (52.8) |
| 2015 | 33 | 16 (48.5) |
| 2016 | 32 | 16 (50.0) |
| 2017 | 46 | 20 (43.5) |
| 2018 | 42 | 20 (47.6) |
| 2019 | 46 | 22 (47.8) |
| 2020 | 36 | 19 (52.8) |
| 2021 | 42 | 15 (35.7) |
| 2022 | 26 | 17 (65.4) |
Conclusions
IHC is increasingly being used for the initial diagnosis of ASC. Furthermore, the use of molecular diagnostics may have led to a pragmatic increase in the diagnosis of ASC.
Legal entity responsible for the study
J. von der Thüsen.
Funding
Has not received any funding.
Disclosure
J. von der Thüsen: Non-Financial Interests, Institutional, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Janssen, MSD, Roche, Roche Diagnostics. All other authors have declared no conflicts of interest.
113P - Clinical overstaging in pathologic stage I non-small cell lung cancer: Prognostic implications
- N. O. Deboever (Houston, United States of America)
- N. O. Deboever (Houston, United States of America)
- M. Eisenberg (Houston, United States of America)
- W. L. Hofstetter (Houston, United States of America)
- R. Mehran (Houston, United States of America)
- R. Rajaram (Houston, United States of America)
- D. Rice (Houston, United States of America)
- S. Swisher (Houston, United States of America)
- G. Walsh (Houston, United States of America)
- A. Vaporciyan (Houston, United States of America)
- B. Sepesi (Houston, United States of America)
- M. Antonoff (Houston, United States of America)
Abstract
Background
Surgery serves a key role in curative therapy for early-stage non-small cell lung cancer (NSCLC), and operative decision-making is heavily dictated by clinical stage. Multiple patient- and disease-specific factors can influence stage assignment in the therapy-naïve patient. As such, discordant clinical and pathological staging may occur, and clinical overstaging may indicate risk of worse outcomes for patients with features that are not otherwise captured in our staging paradigm. Thus, we sought to evaluate the impact of clinical overstaging on overall survival (OS) in patients with pathologic stage I NSCLC who underwent upfront surgery.
Methods
A single-center database was queried for patients who underwent resection of pathologic stage I NSCLC 1998–2021 in the absence of neoadjuvant therapy. Clinicopathologic, circulomic, and operative details were collected. Patients were grouped by clinical-to-pathologic stage concordance to evaluate impact of clinical overstaging on outcomes. Kaplan-Meier and multivariable analyses were performed to assess impact on OS.
Results
2318 patients met inclusion criteria, among whom 151 (6.5%) were clinically overstaged. Slightly over half were women (1355, 58.4%), most were smokers (1649, 71.0%), and median age was 67.0 years (interquartile range [IQR]: 60.1–73.3). In clinically overstaged patients, clinical tumor (T) and nodal (N) statuses were significantly discordant from pathologic T and N status (p < 0.001 for both). Moreover, clinically overstaged patients had shorter median OS (115.4 months) than those with stage-concordance (156.7 months, p < 0.001). After controlling for confounders, we found that clinically overstaged patients experienced greater mortality (hazard ratio 1.34, CI 1.04–1.73).
Conclusions
Clinical overstaging of patients with pathologic stage I NSCLC was associated with worse survival compared concordant staging. This finding may be attributable nto patient and disease factors that prompted assignment of higher clinical stage, and further investigation is needed to better elucidate and ameliorate such factors. Moreover, heightened postoperative cancer surveillance may be indicated for patients found to be clinically overstaged.
Legal entity responsible for the study
The authors.
Funding
Mason Family Philanthropic Research Fund.
Disclosure
All authors have declared no conflicts of interest.
115P - Salvage surgery in patients with locally advanced or metastatic non-small cell lung cancer
- R. S. Werner (Zurich, Switzerland)
- R. S. Werner (Zurich, Switzerland)
- K. Furrer (Zurich, Switzerland)
- O. Lauk (Zurich, Switzerland)
- C. Caviezel (Zurich, Switzerland)
- S. Hillinger (Zurich, Switzerland)
- D. Schneiter (Zurich, Switzerland)
- C. Britschgi (Zurich, Switzerland)
- M. Guckenberger (Zurich, Switzerland)
- I. Opitz (Zurich, Switzerland)
Abstract
Background
In patients with stage IIIB, IIIC and IV non-small cell lung cancer (NSCLC), current guidelines recommend systemic therapy with or without radiotherapy. Despite this treatment, complete response in these stages is rare and median overall survival (mOS) ranges between 6 and 48 months. However, in a selected group of patients with either residual disease after partial response to first-line systemic treatment, or oligo-recurrence, surgical resection within a salvage concept is under evaluation as an additional treatment option. Currently, clinical data on the outcome of this approach are scarce and candidate selection remains challenging. We therefore aimed to assess short- and long-term outcomes of salvage surgery in advanced NSCLC.
Methods
We retrospectively identified 35 patients with initial stage IIIB, IIIC, or IV NSCLC who underwent anatomical lung resection to treat local relapse or residual disease between 2001–2023. All patients had initially received systemic treatment with or without radiotherapy. Patients were only included if surgical resection had not been part of the first-line treatment approach.
Results
Among 35 patients (54% male, mean age 60.2 ± 10.9 years), the initial clinical UICC NSCLC stage was IIIB in 4, IIIC in 4, IVA in 22, and IVB in 5 cases. 17 patients (48.6%) were treated with curative intent and had received radiochemotherapy. The indication for salvage resection was residual disease after first-line treatment in 21 cases (60%) and local relapse in 14 cases (40%). Lung resections included 22 lobectomies (6 sleeve-resections), 11 pneumonectomies, 1 bilobectomy and 1 segmentectomy. R0-resection was achieved in 94.3% and pathological complete response was found in 22.9% of all resections. 30 and 90-day mortality were 0% and 11.4%, respectively. mOS and progression-free survival (calculated from the date of salvage surgery) were 69 months [95% CI 37–101 months] and 22 months [95% CI: 0–45months] respectively.
Conclusions
In selected patients with advanced stage NSCLC presenting with local relapse or residual disease after systemic treatment, anatomical salvage lung resections are associated with a favorable short- and long-term outcome. However, further prospective evaluation of this treatment approach is required.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
I. Opitz: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: Medtronic, Roche; Financial Interests, Institutional, Invited Speaker: Roche. All other authors have declared no conflicts of interest.
116P - Survival outcome of chemotherapy in stage IIIA and IIIB non-small cell lung cancer
- A. S. Aly (Ismailia, Egypt)
- A. S. Aly (Ismailia, Egypt)
- A. Ellaithy (Ismailia, Egypt)
Abstract
Background
About 80% of all lung cancers are non-small cell lung cancer (NSCLC). The early stages are asymptomatic which lead to a late diagnosis. Surgery is the preferred option for stages I and II but the best treatment modality for stages III and IV are chemotherapy and radiotherapy. However, some studies have shown that NSCLC is chemotherapy resistant, which leaves some debates. So, this study aimed to assess the outcome of chemotherapy in stage III cancers.
Methods
Data of 2368 patients was extracted from Surveillance, Epidemiological, and End Results (SEER) database. All of them had stage III non-small cell lung cancer diagnosed from 2000–2019. The classification of stage III was according to eighth edition of AJCC. We divided the patients into four groups; groups who received chemotherapy and groups who had no systemic therapy for stages IIIA and IIIB each. For each group, we calculated relative 5-year survival, and using SPSS 25, we performed Kaplan-Meier curve and log rank test for survival analysis.
Results
The 5-year relative survival for the groups who received chemotherapy for stages IIIA and IIIB and the groups who had no systemic therapy for stages IIIA and IIIB were (23.8%, 18.1%, 7.6%, 6.6% respectively; P < 0.001). The overall survival of sex for stage III was 9.2% for males, and 10.7% for females (P < 0.02). Performing Cox regression model revealed, sex was associated with poor survival outcomes as IIIA (P < 0.001, HR: 1.12, 95%CI: 0.995–1.261) and IIIB (P < 0.001, HR: 1.1, 95%CI: 0.964–1.234,).
Conclusions
Non-small cell lung cancer patients who received chemotherapy showed threefold higher 5-year relative survival compared to the groups who had no systemic therapy. These results also showed that sex is associated with poor survival outcome. So, we recommend chemotherapy to be the first line of treatment for stages IIIA and IIIB for better survival outcome.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
117P - Survival outcomes of surgery-based treatment or definitive chemoradiation with immunotherapy consolidation in stage IIIA NSCLC in the immune therapy era: An NCDB analysis
- J. Sekkath Veedu (Lexington, United States of America)
- J. Sekkath Veedu (Lexington, United States of America)
- Z. Hao (Lexington, United States of America)
- Q. Chen (Lexington, United States of America)
- B. Huang (Lexington, United States of America)
- M. M. Shah-Jadeja (Lexington, United States of America)
Abstract
Background
Stage IIIA non-small cell lung cancer (NSCLC) is a heterogeneous disease treated by a surgery-based approach or definitive chemoradiation (CRT). Surgery is thought to have superior outcomes despite an upfront mortality disadvantage. However, there is no real-world data on outcomes of stage IIIA NSCLC receiving definitive CRT and durvalumab (ICI) consolidation in comparison to surgery-based treatment since durvalumab was introduced.
Methods
We used National Cancer Database (NCDB) to identify 23,110 patients with clinical stage IIIA NSCLC treated with either surgery-based treatment or definitive CRT followed by ICI during 2017–2019, and surgery-based treatment or CRT during 2014–2016. The primary outcome analyzed was overall survival (OS). Kaplan-Meier (KM) plots were used to examine survival curves and Cox regression analysis was used to identify factors associated with OS.
Results
During 2017–2019, surgery consistently had a survival advantage (HR 0.81, 95%CI 0.75–0.88, p < 0.001) across all T and N groups compared to CRT-ICI. Consolidation ICI has improved 3-year OS from 39.1% during 2014–2016 to 56.5% during 2017–2019. A delay of 6+ weeks in initiating ICI after radiation did not confer a negative impact on survival. Lobectomy patients had better OS compared to pneumonectomy. On multivariate analysis, younger age (ages 19–39; HR 0.47, 0.35–0.64); (ages 40–64; HR 0.71, 0.67–0.75); (ages 65–74; HR 0.79, 0.76–0.83); (ages 75+ as HR 1.0), female sex (male sex; HR 1.24, 1.20–1.29; female sex as HR 1.0), non-squamous histology (adenocarcinoma; HR 0.90, 0.86–0.93; squamous histology as HR 1.0) and lower Charlson Comorbidity Index (CCI) (CCI 0; HR 0.81, 0.77–0.85), CCI 1 (HR 0.87, 0.83–0.92); (CCI 2 as HR 1.0), were associated with better OS (p < 0.001).
Conclusions
For stage IIIA NSCLC patients, surgery-based treatment is recommended if operable/resectable. In the first year, surgery has a small survival disadvantage, reflecting the upfront surgical mortality. Using CRT+ICI is slightly inferior to surgery but confers an impressive survival advantage compared with no ICI. Interestingly, delay in ICI did not cause a loss in efficacy.
Legal entity responsible for the study
J. Sekkath Veedu.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
118P - High dose chemo-radio-immunotherapy for NSCLC III: ESR/ATS thresholds for DLCO correlate with radiation dosimetry and predict pneumonitis
- F. Zehentmayr (Salzburg, Austria)
- F. Zehentmayr (Salzburg, Austria)
- B. Grambozov (Salzburg, Austria)
- J. Karner (Salzburg, Austria)
- E. Ruznic (Salzburg, Austria)
- C. Gaisberger (Salzburg, Austria)
- G. Fastner (Salzburg, Austria)
- B. Zellinger (Salzburg, Austria)
- R. Moosbrugger (Salzburg, Austria)
- M. Studnicka (Salzburg, Austria)
- F. Sedlmayer (Salzburg, Austria)
- M. Stana (Salzburg, Austria)
Abstract
Background
Durvalumab following chemoradiotherapy for non-small cell lung cancer (NSCLC) UICC stage III has become the standard of care in the past few years. With this treatment approach 5-year overall survival has risen to 50% for PD/PDL-1-positive patients. Therefore pulmonary function (PF) after treatment is of high importance in long term survivors. In this respect carbon monoxide diffusing capacity (DLCO), which represents the alveolar compartment, was found to be a suitable measure for residual pulmonary capacity. The aim of the current analysis was to correlate pre-treatment DLCO with the occurrence of pneumonitis and to model DLCO decline after therapy to the total radiation dose within a defined lung volume.
Methods
Eighty-five patients with histologically confirmed NSCLC III treated between 2015/10 and 2020/10 were eligible for this study. Patients received two cycles of platinum-based induction chemotherapy followed by high dose radiotherapy and Durvalumab maintenance for one year. The clinical endpoints were based on the thresholds published by the European Respiratory Society. Pre-treatment DLCO of 60% was correlated to the incidence of pneumonitis and DLCO decline of 10% within three months after treatment was related to radiation dose.
Results
Patients with a pre-treatment DLCO below 60% had a higher probability for pneumonitis grade 2 or higher (N = 71, one-sided Pearson correlation coefficient −0.183, p-value 0.063), which became significant in the subgroup of patients without Durvalumab (N = 40, one-sided Pearson correlation coefficient −0.306, p-value 0.027). The decline in DLCO > 10% after the end of radiotherapy depended on the size of the lung volume receiving 45% to 65% (V65%−45%) of the total radiation dose (one-sided Pearson correlation coefficient = 0.264, p-value = 0.019).
Conclusions
The current analysis revealed that DLCO is a predictor for clinically relevant pneumonitis and a monitoring tool for post-treatment lung function as it correlates with radiation dose. This underlines the importance of peri-treatment lung function testing.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
119P - Prospective trial of immuno-(chemo)therapy (IO) prior to resection, definitive chemo-radiotherapy, or palliative therapy in patients with borderline resectable non-small cell lung cancer (NSCLC) including oligometastatic disease (KOMPASSneo)
- M. Faehling (Esslingen am Neckar, Germany)
- M. Faehling (Esslingen am Neckar, Germany)
- K. Lehrach (Esslingen am Neckar, Germany)
- S. Fallscheer (Esslingen am Neckar, Germany)
- B. Schwenk (Esslingen am Neckar, Germany)
- S. Kramberg (Esslingen am Neckar, Germany)
- J. Sträter (Esslingen am Neckar, Germany)
- S. Eschmann (Stuttgart, Germany)
- M. Hetzel (Stuttgart, Germany)
- F. Heinzelmann (Esslingen am Neckar, Germany)
- R. Sätzler (Esslingen am Neckar, Germany)
Abstract
Background
Recent trials of IO prior to resection in locally advanced NSCLC report high rates of pathological response. However, primarily irresectable patients were excluded from most studies. Moreover, there is no data on chemo-radiotherapy (CRT) after IO in patients who are primarily not amenable to CRT. We hypothesized that induction IO may enable more NSCLC patients to receive curative treatment.
Methods
We enrolled 78 patients with borderline resectable NSCLC including oligometastatic disease into a prospective real-world trial of induction IO followed by morphologic and metabolic reassessment and multidisciplinary board-guided curative treatment (resection [preferred] or CRT) or palliative therapy. 1° endpoint was the proportion of patients completing curative treatment. 2° endpoints included response and survival. Furthermore, pathological response was assessed in resected patients. Exploratory endpoints included the predictive role of PD-L1-TPS and the TP53-mutation status.
Results
73 patients (94%) received curative treatment (32 complete resections, 41 CRT). 18 (56%) of resected patients had a major pathological response including 13 (41%) with pathological complete response. In curatively treated patients, there were 23 recurrences (32%) and 15 tumor-related deaths (21%): 5 recurrences (16%) and no deaths in resected patients, and 18 recurrences (44%) and 15 (37%) deaths in CRT-patients (median follow-up 18 months). There were two treatment-related deaths (one postoperative due to sepsis, one after CRT due to pneumonitis). Patients with high PD-L1-TPS had deeper pathological response and longer survival. Resected patients with TP53-mutation had poorer pathological response and numerically more recurrences than those without TP53-mutation.
Conclusions
In patients with borderline resectable NSCLC including oligometastatic disease, induction IO resulted in a high rate of curative treatment with promising survival. Resected patients achieved a high rate of prognostically favorable pathological response.
Clinical trial identification
NCT04926584.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Faehling: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, BMS, MSD; Financial Interests, Institutional, Invited Speaker: MSD, AstraZeneca, Gilead, Roche, Daiichi Sankyo, Mirati, Revolution Medicines. S. Kramberg: Financial Interests, Personal, Invited Speaker: Roche. All other authors have declared no conflicts of interest.
120P - Neoadjuvant immunochemotherapy of pembrolizumab plus chemotherapy in resectable non-small cell lung cancer
- Y. Chen (Tianjin, China)
- Y. Chen (Tianjin, China)
- B. Yan (Tianjin, China)
- J. You (Tianjin, China)
Abstract
Background
Neoadjuvant immunotherapy, as the focus of current research and treatment means for long-term survival, has become one of the options in supporting primary treatment intervention in early NSCLC.
Methods
This was a retrospective analysis of patients with locally resectable NSCLC, who received the neoadjuvant drug pembrolizumab plus chemotherapy and underwent surgical resection. The pathology responses and the PFS and OS in the total sample and subgroups were determined and analyzed. Additionally, artificial intelligence was utilized to incorporate multiple factors for developing a high-performance prediction model.
Results
Of the 61 patients included in the retrospective analysis, 31 (50.82%) patients achieved a pCR, and 38 (62.30%) patients obtained an MPR. For the OS, patients with a pCR were significantly better than the patients with non-pCR (HR, 0.093; P = 0.0227); patients with an MPR performed significantly better than the patients with non-MPR (HR, 0.05357; P = 0.0169). Patients with lymph node metastasis after surgery had significantly worse OS and PFS than those without lymph node metastasis (HR, 0.01607; p = 0.0004; HR, 0.08757; p = 0.0004). The PFS of patients with SCC was better than the patients with non-SCC (HR, 0.3939; p = 0.0340). No significant differences in OS and PFS were found between 2 cycles vs. 3 cycles of neoadjuvant therapy before the surgery; ≤5 cycles vs. >5 cycles of adjuvant therapy post-surgery; TPS of <50% vs. ≥50% (P > 0.05). After model training and optimization, and 5-fold cross-validation, KNC (K-Neighbors Classifier) algorithm was able to predict the pCR with an 85.71% accuracy.
Conclusions
Neoadjuvant immunochemotherapy of pembrolizumab plus chemotherapy for non-small cell lung cancer is safe and tolerable. Both pCR and MPR were closely related to OS and PFS, reflecting the good response of tumor tissues to drug therapy. Lymph node metastasis after surgery was a poor prognostic factor, causing worse OS and PFS. Artificial intelligence constructed a prediction model for assessing treatment efficacy.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
121P - Neoadjuvant sintilimab and anlotinib combined with chemotherapy for resectable NSCLC: A prospective, single arm, multicenter study
- X. Yan (Xi'an, China)
- X. Yan (Xi'an, China)
- H. Duan (xi'an, China)
- T. Wang (Chong Qing, China)
- Z. Luo (Chong Qing, China)
Abstract
Background
To explore the efficacy and safety of neoadjuvant Sintilimab and Anlotinib combined with chemotherapy for resectable NSCLC.
Methods
Before operation, the patients were treated with Sintilimab (200 mg) and Anlotinib (10 mg, po, day 1–14) combined with chemotherapy for 3 cycles, and surgery was performed 4 weeks after the last chemotherapy. After operation, patients were treated with Q3W of Sintilimab (200 mg) for 1 year. Primary end point: Complete pathological response (pCR). Secondary end point: Major pathological response (MPR), safety.
Results
39 patents were included in the study group, including 35 males and 4 females; 30 people with smoking index > 400, 9 people with smoking index < 400; There were 9 cases of adenocarcinoma and 30 cases of squamous cell carcinoma. In addition, 4, 6, 12 and 17 patients in this group were in stages IIA, IIB, IIIA, and IIIB, respectively. Thirty-five patients finally received surgical treatment, one patient refused any treatment due to grade 3 liver damage, and three patients refused surgery after completing neoadjuvant treatment. The pCR of intention to treat (ITT) population is 21 (53.8%), the MPR is 25 (64.1%). The pCR of Per-protocol (PP) population is 60%, and the MPR is 71.4%. According to RECIST 1.1, there was 1 case of progress disease, 9 cases of SD, 27 cases of PR and 2 cases of CR in ITT population. The pCR and ORR of squamous cell carcinoma is much higher than those of adenocarcinoma in ITT or PP population. There were three patients with EGFR mutation (included Exon 19 and L858R) in adenocarcinoma. The incidence rate of AE events above grade 3 related to treatment was 20 (51.3%).
| Patient characteristics (N,%) | |
|---|---|
| Age | |
| ≥60 | 24 (61.5) |
| <60 | 15 (38.5) |
| Sex | |
| Male | 35 (89.7) |
| Female | 4 (10.3) |
| Smoking Index | |
| ≥400 | 30 (76.9) |
| <400 | 9 (23.1) |
| Pathological type | |
| Squamous cell carcinoma | 30 (76.9) |
| Adenocarcinoma | 9 (23.1) |
| Clinical stage | |
| IIA | 4 (10.3) |
| IIB | 6 (15.4) |
| IIIA | 12 (30.8) |
| IIIB | 17 (43.5) |
| Pathological response | |
| PCR(ITT) | 21 (53.8) |
| MPR(ITT) | 25 (64.1) |
| PCR(PP) | 21 (60.0) |
| MPR(PP) | 25 (71.4) |
| Squamous cell carcinoma (PCR-PP, N = 26) | 19(73.1) |
| Squamous cell carcinoma (MPR-PP, N = 26) | 23(88.5) |
| Adenocarcinoma (PCR-PP, N = 9) | 3 (33.3) |
| Adenocarcinoma (MPR-PP, N = 9) | 3 (33.3) |
| RECIST 1.1 | |
| ORR(ITT) | 29 (74.4) |
| ORR(PP) | 25 (71.4) |
| Squamous cell carcinoma (ORR-PP, N = 26) | 21 (80.8) |
| Adenocarcinoma (ORR-PP, N = 9) | 5 (55.6) |
Conclusions
The neoadjuvant treatment of Sintilimab and Anlotinib combined with chemotherapy can significantly increase the pCR of resectable NSCLC, which is an effective treatment method. However, the perioperative AE events should be paid attention to.
Clinical trial identification
NCT05400070.
Legal entity responsible for the study
The authors.
Funding
The National Natural Science Foundation of China (No. 81871866) Miaozi Talent Fund of Tangdu Hospital of Air Force Military Medical University.
Disclosure
All authors have declared no conflicts of interest.
122P - Comparison of the efficacy of neoadjuvant pembrolizumab vs sintilimab combination with chemotherapy in resectable lung cancer: A multicenter propensity score matching study
- X. Yan (Xi'an, China)
- X. Yan (Xi'an, China)
- H. Duan (xi'an, China)
Abstract
Background
This study aims to evaluate the effectiveness of using Pembrolizumab or Sintilimab combined with chemotherapy in NSCLC treatment using the Propensity Score Matching (PSM) analysis.
Methods
The NSCLC patients were treated with neoadjuvent Pembrolizumab or Sintilimab combined with chemotherapy in two hospitals since June 2018. The objective response rate (ORR), pathological complete response (pCR), and operation-related information of the two groups were analyzed by PSM analysis.
Results
Here, 116 patients were enrolled in the study, where 61 were classified into the Sintilimab group while 55 were included in the Pembrolizumab group. The results indicated that 28 patients (45.9%) in the Sintilimab group achieved pCR while 30 patients (54.5%) in the Pembrolizumab group showed pCR(P = 0.353). No significant differences were noted in MPR between the Sintilimab and Pembrolizumab groups (39, 63.9% vs 36, 65.5%, P = 0.861). Furthermore, the ORR values showed no statistically significant differences between the groups when compared to the assessment of the effects by the Sintilimab and the Pembrolizumab groups (46, 75.4% vs. 44, 80.0%, P = 0.554). There was no discernible difference in ORR and pCR values between the two groups after the first and second PSM analyses. After a Logistic analysis, before and after PSM, treatment with ≥3 cycles were still regarded as the promoting factor of pCR.
| Sintilimab (n = 61) | Pembrolizumab(n = 55) | P | |
|---|---|---|---|
| Sex | 0.493 | ||
| Male | 53(86.9) | 50(90.9) | |
| Female | 8(13.1) | 5(9.1) | |
| Age | 0.864 | ||
| ≥60 | 39(63.9) | 36(65.5) | |
| <60 | 22(36.1) | 19(34.5) | |
| BMI | 0.001 | ||
| ≥24 | 12(19.7) | 26(47.3) | |
| <24 | 49(80.3) | 29(52.7) | |
| Smoking Index | 0.07 | ||
| ≥400 | 48(78.7) | 40(72.7) | |
| <400 | 13(21.3) | 15(27.3) | |
| Pathological type | 0.069 | ||
| Squamous cell cancer | 45(73.8) | 48(87.3) | |
| Adenocarcinoma Cycles of neoadjuvant therapy | 16(26.2) | 79(12.7) | |
| ≤2 | 30(49.2) | 12(21.8) | |
| ≥3 | 31(50.8) | 43(78.2) | |
| Clinical stage | 0.670 | ||
| I, II | 14(22.9) | 11(20.0) | |
| III | 47(77.1) | 44(80.0) | |
| RECIST 1.1 evaluation | 0.554 | ||
| ORR | 46(75.4) | 44(80.0) | |
| NON-ORR | 15(25.6) | 11(20.0) | |
| Pathlogical evaluation | 0.353 | ||
| pCR | 28(45.9) | 30(54.5) | |
| NON-pCR | 33(54.1) | 25(45.5) |
Conclusions
Sintilimab or Pembrolizumab combined with chemotherapy display a similar pCR to the neoadjuvant treatment of resectable NSCLC. So these both PD-1 inhibitors could show similar effects in NSCLC treatment.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
123P - Second progression-free survival (PFS2) after first progression in patients receiving PACIFIC regimen: An exploratory analysis of the Blue Sky observational study
- A. R. Filippi (Pavia, Italy)
- A. R. Filippi (Pavia, Italy)
- J. Saddi (Pavia, Italy)
- F. Agustoni (Pavia, Italy)
- G. Galli (Pavia, Italy)
- S. La Mattina (Pavia, Italy)
- G. Facheris (Brescia, Italy)
- S. Arcangeli (Milano, Italy)
- D. L. Cortinovis (Monza, Italy)
- G. Piperno (Milan, Italy)
- M. Zerella (Milan, Italy)
- A. Becchetti (Perugia, Italy)
- L. Falcinelli (Perugia, Italy)
- G. Stella (Pavia, Italy)
- C. Bortolotto (Pavia, Italy)
- A. Ferrari (Pavia, Italy)
- P. Pedrazzoli (Pavia, Italy)
- L. Preda (Pavia, Italy)
- P. Borghetti (Brescia, Italy)
Abstract
Background
The Blue Sky Radiomic trial is a multicenter, observational, retrospective, and prospective study started in 2020, with a target sample size of 100 patients with unresectable stage III A-C NSCLC treated with the PACIFIC regimen (
Methods
All patients were deemed unresectable by MTB and had PD-L1-positive (>1%) tumors, with at least stable disease, and receiving one durvalumab dose after CRT; 93/100 pts were evaluable, with 56 recorded events (6 deaths and 50 progressions). PFS2 was calculated for these 50 pts from the date of first to second progression or death (Kaplan-Meier).
Results
At a median follow-up time of 18 months, the median PFS of the entire cohort was 23.2 months (2.10–47.63). Median OS was not reached. Among patients experiencing a first PD (n = 50), 9 pts (18%) relapsed within the first 3 months from durvalumab start, 10 (20%) between 3 and 6, and 31 (62%) after 6 months. The pattern of relapse was as follows: 16 local recurrences (32%), 17 distant progressions (34%), and 17 both (34%), respectively. Forty-one/50 (82%) patients did receive an active treatment at the first progression: 22 pts systemic therapy (53.6%, 9 pts a platinum-based doublet, 11 mono-CT, 1 IO, and 1 TKI); 10 RT alone (24.4%); 6 CT plus local treatment (14.6%), and 3 metastasectomies alone (7.4%). With a median follow-up of 5.33 months (1.07–32.43) from the first PD, we recorded 29 deaths. Ten pts are alive without progression, and 11 are alive with progressive disease. Median PFS2 was 7.23 months (1.03–42), and median OS was 15.5 months (1.07–46.17), respectively.
Conclusions
This exploratory analysis suggests that most progressing patients can receive subsequent therapy at the time of first progression following CRT plus durvalumab in a real-world setting. The median PFS2 of around 7 months could be used as a reference for the design of future trials.
Clinical trial identification
NCT04364776.
Legal entity responsible for the study
Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Funding
Fondazione IRCCS Policlinico San Matteo, Ricerca Corrente 2019.
Disclosure
A.R.R. Filippi: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche; Financial Interests, Institutional, Sponsor/Funding: MSD, Roche, AstraZeneca; Financial Interests, Personal, Speaker's Bureau: Ipsen. G. Piperno: Financial Interests, Personal, Speaker's Bureau: AstraZeneca. All other authors have declared no conflicts of interest.
124P - SPOTLIGHT real-world study: Outcomes with or without consolidation durvalumab (D) after chemoradiotherapy (CRT) in patients with unresectable stage III NSCLC
- R. M. Whitaker (Nashville, United States of America)
- R. M. Whitaker (Nashville, United States of America)
- L. Cai (Gaithersburg, United States of America)
- A. Wang (Gaithersburg, United States of America)
- Y. Qiao (Gaithersburg, United States of America)
- P. Chander (Gaithersburg, United States of America)
- M. Mooradian (Boston, United States of America)
Abstract
Background
PACIFIC established D as the standard of care for patients (pts) with unresectable Stage III NSCLC and no progression after CRT. In retrospective observational studies, such as PACIFIC-R (Girard, 2022), outcomes in pts who re