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Presentation Topic- Advanced NSCLC
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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.