1421P - EGFR inhibition in EGFR-amplified esophagogastric cancer (EGC): Retrospective global experience

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

*Concurrent nivolumab in 2 pts.

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.

Clinical trial identification

Editorial acknowledgement

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.