Background

Phase III evaluation of EGFR inhibition (EGFRi) in unselected EGC patients failed to demonstrate survival benefit. However, subset analyses identified improved outcomes in patients (pts) with EGFR-amplified EGC (6%). We therefore sought to evaluate the retrospective experience of EGFRi in EGFR-amplified EGC.

Methods

We retrospectively identified pts with histologically-confirmed EGC in the metastatic or unresectable setting whose tumors were EGFR-amplified and who received on- or off-protocol EGFRi at 13 tertiary centers in the U.S., U.K., Italy, Korea, Japan, and Turkey. Testing could be by tissue-next generation sequencing (NGS), cell-free DNA (cfDNA)-NGS, or fluorescence in-situ hybridization (FISH) performed by a CLIA-approved laboratory.

Results

Fifty-six pts received cetuximab (n=26), ABT-806 (n=13), panitumumab (n=10), gefitinib (n=5), or cetuximab + TKI (n=2), and 29 (52%) patients received concurrent chemotherapy. Pts received therapy in the 1st (36%), 2nd (23%) or 3+ (42%) treatment line. At the time of censoring, 8 of 56 patients (14%) remain on therapy. Twenty-one of 50 (42%) evaluable pts achieved an objective response (Table). The median duration of response was 4.4 months (range 1.2-16.1 months). Median progression-free survival (mPFS) was 6.4 months (95% CI 6.0-9.8) with concurrent chemotherapy and 2.7 months (95% CI 2.0-5.3) without. PFS varied by EGFRi - 7.8, 6.4,3.0, and 2.0 months for cetuximab, ABT-806, gefitinib, and panitumumab, respectively. Four of 8 pts with progression as best overall response had baseline MET or ERBB2 co-amplifications. Correlation of baseline RAS/RAF/PIK3CA alterations and clinical benefit will be presented. Table: 1421P

Objective response by line

Conclusions

Pts with EGFR-amplified EGC derive clinical benefit from EGFR inhibition, which is most pronounced in the absence of intrinsic resistance mechanisms. An upcoming trial of amivantamab in EGFR and/or MET amplified EGC is planned.

Legal entity responsible for the study

Steven B. Maron.

Funding

Has not received any funding.

Disclosure

S. Maron: Financial Interests, Personal, Advisory Board: Basilea; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Natera; Financial Interests, Personal, Stocks/Shares: Calithera; Non-Financial Interests, Institutional, Other: Guardant Health; Non-Financial Interests, Institutional, Other: Genentech. G. Ku: Financial Interests, Personal, Advisory Board: Apexigen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pieris; Financial Interests, Personal, Advisory Board: Zymeworks. P.M. Kasi: Financial Interests, Personal, Advisory Board: Foundation Medicine; Financial Interests, Personal, Advisory Board: Natera; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Merck MSD. N. Uboha: Financial Interests, Institutional, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal and Institutional, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Board: AstraZenecca; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: QED; Financial Interests, Personal, Stocks/Shares: Natera; Financial Interests, Personal, Stocks/Shares: Exact Science. S. Kato: Financial Interests, Personal, Advisory Role: Foundation Medicine; Financial Interests, Personal, Advisory Role: Neogenomics; Financial Interests, Personal, Advisory Role: CureMatch; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Institutional, Funding: ACT Genomics; Financial Interests, Institutional, Funding: Sysmex; Financial Interests, Institutional, Funding: Konica Minolta; Financial Interests, Institutional, Funding: OmniSeq. K. Shitara: Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: AbbVie; Financial Interests, Personal, Other: Yakult; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Bristol-Meyers Squibb; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Dainippon; Financial Interests, Institutional, Research Grant: Sumitomo Pharma; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Chugai Pharm; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: Medi Science; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Personal, Advisory Role: Taiho; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Glaxo Smith Kline; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim. Y. Nakamura: Financial Interests, Institutional, Research Grant: Genomedia; Financial Interests, Institutional, Research Grant: Guardant Health; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Chugai. J. Chao: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Macrogenics; Financial Interests, Personal and Institutional, Invited Speaker: Merck; Financial Interests, Personal, Advisory Role: Ono Pharmaeuticals; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Board: Turning Point Therapeutics; Financial Interests, Institutional, Funding: Brooklyn Immunotherapeutics. J. Lee: Financial Interests, Personal, Advisory Role: Mirati; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Oncologie; Financial Interests, Personal, Advisory Role: AstraZeneca. Z. Wainberg: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Five Prime; Financial Interests, Personal, Advisory Role: Gilead; Financial Interests, Personal, Advisory Role: Arcus; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Molecular Templates; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Daiicchi; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Ipsen; Financial Interests, Institutional, Invited Speaker: Five Prime; Financial Interests, Institutional, Invited Speaker: GIlead; Financial Interests, Institutional, Invited Speaker: Arcus; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: Molecular Templates; Financial Interests, Institutional, Invited Speaker: Roche/Genentech; Financial Interests, Institutional, Invited Speaker: Array. R. Petty: Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Five Prime; Financial Interests, Institutional, Research Grant: Clovis; Financial Interests, Institutional, Research Grant: Boston Biomedical; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Basilea; Financial Interests, Institutional, Research Grant: Sanofi. S.J. Klempner: Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Natera; Financial Interests, Personal, Advisory Role: Pieris; Financial Interests, Personal, Stocks/Shares: Turning Point Therapeutics; Non-Financial Interests, Institutional, Principal Investigator: Leap Therapeutics; Non-Financial Interests, Institutional, Principal Investigator: Astellas; Non-Financial Interests, Institutional, Principal Investigator: Macrogenics; Non-Financial Interests, Personal, Advisory Board: Debbie's Dream Foundation; Non-Financial Interests, Personal, Advisory Board: Hope for Stomach Cancer; Non-Financial Interests, Personal, Leadership Role: NCCN. D.V. Catenacci: Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Five Prime; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Taiho; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Pieris; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Zymeworks; Financial Interests, Personal, Advisory Role: QED; Financial Interests, Personal, Advisory Role: Gritstone; Financial Interests, Personal, Advisory Role: Foundation Medicine; Financial Interests, Personal, Advisory Role: Tempus; Financial Interests, Personal, Advisory Role: Guardant Health; Financial Interests, Personal, Advisory Role: Natera; Financial Interests, Personal, Advisory Role: Archer; Financial Interests, Personal and Institutional, Advisory Role: Genentech/Roche; Financial Interests, Personal and Institutional, Advisory Role: Amgen; Non-Financial Interests, Institutional, Principal Investigator: Macrogenics; Non-Financial Interests, Institutional, Principal Investigator: AbbVie. All other authors have declared no conflicts of interest.