Abstract 655P
Background
MET amplification is a resistance mechanism to EGFR-TKI. It is reported in 7 to 20% of NSCLC pretreated with EGFR-TKIs. De novo MET amplification in EGFR mutant NSCLC is uncommon. We report the frequency of MET amplification among patients with advanced EGFR mutant NSCLC, along with clinicopathological characteristics and clinical outcomes of this population.
Methods
We reviewed 1,945 NSCLC patients with EGFR mutation in the Lung Cancer Consortium Singapore database. Patients with de novo MET amplification were included in this analysis. Patient characteristics, time-to-treatment failure, and overall survival were analyzed. MET amplification was detected by FISH or next-generation sequencing.
Results
From 2012 to 2020, de novo MET amplification was identified in 0.98% (19 out of 1,945) of EGFR-mutant NSCLC patients. The median age was 57 years old (46 – 80), 10 patients (52.6%) were male, and 16 (84.2%) were never smokers. Ten patients received first-generation (1G), 8 received second-generation (2G), and 1 received third-generation (3G) EGFR-TKIs. The median time to treatment failure (TTF) was 12.6 months (9.2 months, 10.7 months, and 13.5 months for 1G, 2G, and 3G EGFR-TKI, respectively). The median overall survival (OS) was 22.4 months (19.5 months, 27.1 months, and 15.5 months for 1G, 2G, and 3G EGFR-TKI, respectively). The overall response rate (ORR) was 68.4% (13 PR, 1 SD, and 5 PD).
Conclusions
In our dataset, almost 1% of EGFR-mutant NSCLC harbor de novo MET amplification. Most patients received 1G or 2G EGFR-TKI. The PFS, OS, and ORR were slightly lower than published data on first-line EGFR-TKI. These findings underscore the need for routine MET testing in EGFR-mutant NSCLC and support the exploration of combinatory therapeutic approaches integrating MET inhibitors or chemotherapy alongside EGFR inhibition to overcome resistance and improve patient outcomes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Lung Cancer Consortium Singapore.
Funding
Has not received any funding.
Disclosure
D.D.W. Lee: Financial Interests, Personal, Invited Speaker: Pfizer, Takeda, Zuellig Pharma, Ipsen, Roche, MSD, Juniper Biologics, AstraZeneca; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal and Institutional, Local PI: Beigene. G. Lai: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Local PI: AstraZeneca, Amgen, Pfizer, BMS, Roche; Other, Personal, Other, sponsorship for meeting: DKSH. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche, Regeneron, Genmab; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Steering Committee Member: Novartis. All other authors have declared no conflicts of interest.