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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.