Abstract 690P
Background
METamp is a common resistance mechanism to osimertinib in advanced EGFRm NSCLC. While single arm phase II studies show that osimertinib combined with a MET inhibitor (METi) is effective, no randomized studies compare osimertinib/METi with chemotherapy. This study reports clinical outcomes for EGFRm NSCLC patients (pts) with METamp after osimertinib resistance.
Methods
This multicenter retrospective study enrolled pts with advanced EGFRm NSCLC and METamp who experienced disease progression on osimertinib, treated outside clinical trials between October 2021 and January 2024. Study endpoints included time-to-treatment failure (TTF), objective response rate (ORR), and overall survival (OS) post-osimertinib failure with osimertinib plus METi versus platinum-based chemotherapy (PbChT).
Results
38 pts from four institutions were analyzed. Pts aged 33-80 years, all Asians, with 21 females, all having adenocarcinoma histology. Osimertinib was used as 1st line in 23 pts (60%) and 2nd line in 15 pts (40%). METamp was diagnosed through tissue genotyping in 33 cases (26 by NGS, 9 by FISH) and liquid biopsy NGS in 7 cases. After osimertinib failure, 22 pts received osimertinib plus METi (savolitinib, tepotinib, capmatinib, or crizotinib), and 16 received PbChT. Clinical characteristics were similar between groups. Median follow-up durations were 9.4 months for the osimertinib/METi and 10.8 months for PbChT. Median TTF was longer with osimertinib/METi (11.5 months, 95% CI 7.6-15.4) compared to PbChT (2.4 months, 95% CI 1.9-2.8) (HR 0.13, p<0.001). ORR was higher with osimertinib/METi (89%, 16/18) than PbChT (33%, 5/15) (p=0.001). Pts on osimertinib/METi had improved medial OS (27.4 months, 95% CI 8.3-46.4) compared to PbChT (7.9 months, 95% CI 2.5-13.2) (HR 0.22, p=0.007), despite 7 pts receiving osimertinib/METi after progression on PbChT. ILD was reported in 4 pts (14%) on osimertinib/METi (2 grade 2, 2 grade 3-4).
Conclusions
Osimertinib plus METi was effective and improved survival in EGFRm NSCLC pts with METamp after osimertinib resistance. Ongoing randomized phase III studies (e.g. SAFFRON) are evaluating this combination.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L.L. Chan: Financial Interests, Personal, Sponsor/Funding: Roche, AstraZeneca, Ipsen. K.C.K. Yan: Non-Financial Interests, Personal, Speaker’s Bureau: Wolters Kluwer; Non-Financial Interests, Personal, Sponsor/Funding: MSD, Leo Pharma. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: ACEA Pharma, AbbVie, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Daz Group, Eli Lilly, Fishawack Facilitate, InMed Medical Communication, Janssen Pharmaceutical NV, Jiahui Holdings Co., LiangYiHui Healthcare, Lucence Health Inc., Lunit USA, Inc., MD Health, MSD, Medscape/WebMD, Merck Pharmaceuticals HK Ltd, Merck Serono, MiRXES, Novartis, OrigiMed Co. Ltd., PER, PeerVoice, Permanyer SL, Pfizer, Prime Oncology, Research to Practice, Roche, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Ltd., Shanghai Promedican Pharmaceuticals Co., Ltd, Taiho Pharmaceutical Co., Ltd, Takeda, Touch Medical Media; Financial Interests, Personal, Advisory Board: ACEA Pharma, AbbVie, Alpha Biopharma, Amgen, Amoy Diagnostics, Bayer Healthcare Pharmaceuticals Ltd., BeiGene, BerGenBio ASA, Berry Oncology, Berry Oncology, Blueprint Medicines, Boehringer Ingelheim, Bowtie Life Insurance Co Ltd, Bristol Myers Squibb, C4 Therapeutics, CStone Pharma, Cirina Ltd., Covidien LP, Curio Science, D3 Bio Ltd., Da Volterrra, Daiichi Sankyo, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd / Genentech, Fishawack Facilitate, G1 Therapeutics, Gilead Sciences, Gritstone Oncology, Guardant Health, Hengrui, IQVIA, Ignyta, Imagene AI Ltd, Incyte Corporation, Inivata, Janssen, Lakeshore Biotech, Loxo Oncology, Lucence Health Inc., Lunit USA, Inc., MSD, Medscape LLC / WebMD, Merck Serono, MiRXES, Mirati Therapeutics, MoreHealth, Novartis, OSE Immunotherapeutics, OrigiMed, Pfizer, Prenetics Global Limited, Puma Tech., Qiming Dev., Regeneron Pharmaceuticals Inc., Roche, SFJ Pharmaceutical Ltd., Sanofi-Aventis, Simcere Zaiming, Inc, Simcere of America Inc, Synergy Research, Takeda, Tigermed, Vertex Pharmaceuticals, Virtus Medical, Yuhan Corporation; Financial Interests, Personal, Other, consultation services: AVEO Pharmaceuticals, Inc, Alentis Therapeutics AG, BerGenBio ASA, Bridge Biotherapeutics Inc, Elevation Oncology, GLG’s Healthcare, Genentech, Illumina, Inc., Novocure GmbH, Phanes Therapeutics, geneDecode Co., Ltd; Financial Interests, Personal, Other, Consultation services: Adagene, XENCOR, Inc; Financial Interests, Personal, Other, Consultation Services: HiberCell, Inc., Seagen International GmbH, AnHeart Therapeutics Inc, Ningbo NewBay Technology Development Co., Ltd., InxMed (Hong Kong) Limited; Financial Interests, Personal, Other, Consultant Services: Schrödinger, Inc; Financial Interests, Personal, Member of Board of Directors: AstraZeneca, Aurora, Insighta; Financial Interests, Personal, Member of Board of Directors, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Personal, Stocks/Shares, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Personal, Stocks/Shares: Biolidics Ltd., Aurora Tele-Oncology, AstraZeneca, D3 Bio, Lunit Inc., Precentics, Alentis Therapeutics AG; Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology; Non-Financial Interests, Personal, Advisory Role: geneDecode; Non-Financial Interests, Personal, Other, Invited Speaker: AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc.; Non-Financial Interests, Personal, Leadership Role, Term ended: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Personal, Leadership Role, Term ended on 30 June 2022: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Personal, Leadership Role: Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen’s College & Prep. School (Hong Kong); Non-Financial Interests, Personal, Leadership Role, Term ended on 30 April 2019: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Personal, Leadership Role, Honorary Secretary, from Dec 2022 - Present: Hong Kong Academy of Sciences. S.C.M. Li: Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Novartis, Amgen, Pfizer, Takeda, ACE Oncology, Gilead, Guardant Health, Janssen, Merck, MSD, BMS; Financial Interests, Personal, Sponsor/Funding: AstraZeneca, Pfizer, Daiichi Sankyo, MSD, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Takeda, Amgen, AnHeart Therapeutics, Yuhan; Non-Financial Interests, Personal, Advisory Board: Blossomhill Therapeutics. All other authors have declared no conflicts of interest.