Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression and biomarker overlap in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC)

BackgroundFGFR2b protein is emerging as a potential therapeutic target in patients with advanced GC/GEJC. This study investigated the estimated prevalence of FGFR2b protein overexpression and its overlap with actionable biomarkers.MethodsTumor samples from 130 Japanese patients diagnosed with advanced/metastatic GC/GEJC between 01 January 2021 and 31 October 2022 were analyzed. FFPE samples collected before 1L were tested via immunohistochemistry (IHC) for FGFR2b [clone FPR2-D] and PD-L1 [clone 28-8]. HER2, MMR and Claudin 18 [clone 43-14A] expression were also assessed. FGFR2b overexpression was defined as any percentage of tumor cells exhibiting moderate (2+) to strong (3+) membranous staining (FGFR2b any 2+/3+). FGFR2b overexpression of ≥10% of tumor cells exhibiting 2+ to 3+ membranous staining (FGFR2b ≥10% 2+/3+) was also evaluated.ResultsEstimated prevalence of FGFR2b any 2+/3+ was 29% (95% CI: 22, 39) and of FGFR2b ≥10% 2+/3+ was 11% (95% CI: 6, 17). In HER2 negative FGFR2b any 2+/3+ tumor samples, 16% exhibited a PD-L1 CPS ≥ 5 and 36% expressed Claudin 18 in ≥75% of tumor cells at 2+ or 3+ staining. For HER2 negative FGFR2b ≥10% 2+/3+ tumor samples, those proportions were 14% and 43%, respectively. Select biomarker overlap is summarized in the table. Table: 1420P Overlap of HER2, PD-L1, MMR, Claudin 18, and FGFR2b in advanced or metastatic G/GEJ cancer tumor samples from a Japanese cohort Within HER2 Negative Total HER2 positive HER2 negative PD-L1 CPS <5 PD-L1 CPS ≥5 MMR deficient MMR proficient Claudin 18 <75% 2+/3+ Claudin 18 ≥75% 2+/3+ Full Cohort % (n) 100% (130) 20% (26) 80% (104) 64% (66) 36% (37) 3% (3) 97% (101) 66% (69) 34% (35) FGFR2b any 2+/3+ % (n) 29% (38) 13% (5) 87% (33) 84% (27) 16% (5) 0% (0) 100% (33) 64% (21) 36% (12) FGFR2b ≥ 10% 2+/3+ % (n) 11% (14) 0% (0) 100% (14) 86% (12) 14% (2) 0% (0) 100% (14) 57% (8) 43% (6) One sample was unevaluable for PD-L1 but FGFR2b any 2+/3+. Percentages are row percentages except for the “Total� column. ConclusionsThis real-world study estimated the prevalence of FGFR2b protein overexpression in GC/GEJC, revealing limited overlap with currently actionable biomarkers such as PD-L1 and Claudin 18 in tumor samples from a Japanese cohort.Legal entity responsible for the studyAmgen Inc.FundingAmgen Inc.DisclosureS.L. Rhodes, E. Finger, C. Chang, R.E. Yanes, H. Honeycutt: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks or ownership: Amgen. Y. Aoki: Financial Interests, Personal, Invited Speaker: Guardant Health Inc. I. Nakayama: Financial Interests, Institutional, Local PI: Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, MSD. Y. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Guardant Health Pte Ltd., MSD K.K, Eisai, Zeria Pharmaceutical, Miyarisan Pharmaceutical, CareNet, Inc., Hisamitsu Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo Co., Ltd., Becton Dickinson, Guardant Health Japan Corp.; Financial Interests, Personal, Advisory Board: Natera, Inc., Roche Ltd., Seagen, Inc., Premo Partners, Inc., Daiichi Sankyo Co., Ltd., Takeda, Exact Sciences, Gilead Sciences, Guardant Health Pte Ltd; Financial Interests, Institutional, Funding: Taiho, Chugai, Guardant Health, Genomedia, Daiichi Sankyo, Roche Diagnostics, Guardant Health AMEA, Inc., Tempus; Financial Interests, Institutional, Coordinating PI: Seagen. A. Kawazoe: Financial Interests, Personal, Advisory Board: Zymeworks, Merck & Co.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eli Lilly, Bristol Myers Squibb, Ono Pharmaceutical Co., Ltd. D. Kotani: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Merck Biopharma, Ono pharma, Pfizer, Taiho pharma, Takeda, Sysmex, Nihonkayaku, Novartis, Guardant Health; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Local PI: Ono pharma, MSD, Servier, Novartis, Janssen pharma, IQVIA, Syneos Health, CIMIC Shiftzero, CIMIC; Financial Interests, Institutional, Funding: Ono pharma. Y. Kuboki: Financial Interests, Personal, Advisory Board: Takeda, Amgen, Abbie, Incyte, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Taiho, Lilly; Financial Interests, Institutional, Local PI: Taiho, Astellas, Lilly, Takeda, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, Incyte, Abbie, Merck, Novartis, Hengrui; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, Member: JSMO, ASCO, JSCO, JCA. H. Bando: Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Other, Lecture fee: Ono Pharmaceutical, Taiho Pharmaceutical, Eli Lilly Japan. T. Kojima: Financial Interests, Personal, Invited Speaker: MSD, Bristol Myers Squibb, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Kyowa Kirin, Taiho Pharmaceutical; Financial Interests, Institutional, Local PI: AstraZeneca, BeiGene, MSD, Amgen, Chugai Pharmaceutical, Taiho Pharmaceutical, Shionogi Pharma, Amgen Astellas BioPharma. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd., Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., FALCO Biosystems Ltd., Merus N.V., Bristol Myers Squibb K.K., Medical & Biological Laboratories Co., LTD., Takeda Pharmaceutical Co., Ltd. K. Shitara: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Takeda, Ono Pharmaceutical, MSD, Novartis, Daiichi Sankyo, Amgen, Guardant Health Japan Corp, Astellas Pharma Inc., Astellas, Bayer, AstraZeneca, Zymeworks Biopharmaceuticals Inc., ALX Oncology Inc.; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Janssen, AstraZeneca, Eli Lilly, Astellas, Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, MSD, Eisai, Amgen, PRA Health Sciences. All other authors have declared no conflicts of interest.