149P - A prospective observational study of MSI screening in unresectable chemotherapy-naïve advanced gastric cancer/gastroesophageal junction cancer: WJOG13320GPS

Background

Microsatellite instability-high (MSI-H) is one of the biomarkers for response to anti-PD-1 antibody for solid tumors including gastric cancer (GC) or gastroesophageal junction cancer (GEJC). Characteristics of patients with MSI-H G/GEJC are not well-known. We conducted a prospective observational study as screening for WJOG13320G, a single arm phase 2 trial of Nivolumab plus low dose Ipilimumab (jRCT2080225304), and to clarify the prevalence and clinicopathological features of chemotherapy-naïve MSI-H advanced G/GEJC.

Methods

Key inclusion criteria were following; histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of stomach or GEJ, ECOG PS of 0 or 1, age of at least 20 years, no prior systemic anticancer therapy for advanced or metastatic disease and adequate organ function. Formalin-fixed paraffin-embedded tissue from biopsy or surgical specimens was used for the MSI-IVD Kit (FALCO). The primary endpoint was the proportion of patients with MSI-H in chemotherapy-naïve G/GEJC and a key secondary endpoint was clinicopathological features of MSI-H advanced G/GEJC.

Results

Between Oct. 2020 and Oct. 2022, 935 patients from 75 centers in Japan were registered. Because of 2 withdrawal and 3 ineligible, 930 patients were analyzed. The male: female ratio was 69:31 and median age was 70 (range; 24-88) years. All specimens were successfully tested, with a median turn-around-time of 7 (range; 3-37) days. The proportion of MSI-H G/GEJC was 5.6 (95% CI; 4.2-7.3) %. MSI-H was more frequent in female (9.6%) than in male (3.8%; p<0.01), in lower stomach (10.5%) than in upper/middle stomach or GEJ (2.1/3.7/4.0%; p<0.01), in patients without liver metastases (6.9%) than in those with liver metastases (2.2%, p<0.01) and in HER2-negative (6.5%) than in HER2-positive (1.8%, p=0.02). The median age was higher in MSI-H patients (74 years) than in non-MSI-H patients (70 years, p<0.01).

Conclusions

The proportion of MSI-H in unresectable chemotherapy-naïve advanced G/GEJC was 5.6%. MSI-H G/GEJC was characterized by female, older age, lower stomach, no liver metastases, and HER2-negative.

Clinical trial identification

UMIN000040366.

Editorial acknowledgement

Legal entity responsible for the study

West Japan Oncology Group.

Funding

Bristol Myers Squibb Company, FALCO biosystems Ltd.

Disclosure

Y. Narita: Financial Interests, Personal, Invited Speaker: Yakult, Taiho, Eli Lilly, Daiichi Sankyo, Ono pharma, BMS; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Local PI: Ono pharma, BMS, AstraZeneca, Diaiichi Sankyo. S. Hironaka: Financial Interests, Personal, Other, lecture: Ono Pharm, BMS, Eli Lilly, Taiho, Daiichi Sankyo, MSD, Chugai, Merck Biopharma, Takeda, Yakult Honsha. H. Kawakami: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd., Bayer Yakuhin Ltd, Eli Lilly Japan K.K., MSD K.K., Chugai Pharmaceutical Co. Ltd., Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co. Ltd., Yakult Pharmaceutical Industry, Teijin Pharma Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Other, Lecture: GSK K.K, Otsuka Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant, Investigator-Initiated Trial: Bristol Myers Squibb Co. Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co. Ltd, Eisai Co., Ltd., Kobayashi Pharmaceutical Co. Ltd., PAREXEL International Corp., PRA HEALTHSCIENCES, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co., Ltd,., MSD K.K., Ono Pharmaceutical Co., Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services JAPAN K.K., Syneos Health Clinical K.K., Nippon Kayaku Co., Ltd., EP-CRSU Co., Ltd., Eisai Co., Ltd., Mebix, Inc., Bristol Myers Squibb K.K., Janssen Pharmaceutical K.K., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., GSK K.K., Sanofi K.K., Nippon Boehringer Ingelheim Co., Ltd., Sysmex Corporation, Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., SRL, Inc., Daiichi Sankyo Co., Ltd., Amgen Inc., Medical Reserch Support, Eli Lilly Japan K.K. M. Furuta: Financial Interests, Personal, Invited Speaker: Eli Lilly, Bristol Myers Squibb, Merck & Co., Inc., Ono Pharmaceutical CO., LTD., Takeda Pharmaceutical Company Limited. T. Kawakami: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, honoraria: Bristol Myers Squibb, Ono Pharmaceutical, Yakult Honsha, Daiichi Sankyo. A. Makiyama: Financial Interests, Personal, Invited Speaker: Eli Lilly, Taiho, Ono, Daiichi Sankyo, Bristol Myers Squibb. H. Hirano: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Ono Pharmaceutical, Teijin Phama, Novartis; Financial Interests, Personal, Writing Engagement: Nichi-Iko; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Ono Pharmaceutical, Janssen Pharmaceutical, Merck Biopharma, Bristol Myers Squibb, Pfizer, Eisai, Amgen, Astellas, Seagen, MSD, Insyte, BeiGene, Novartis. M. Komoda: Financial Interests, Personal, Invited Speaker: Lilly Japan, Ono Pharmaceutical, Bristol Myers Squibb Japan, Eisai, Daiichi Sankyo/UCB Japan, Chugai Pharma, Taiho Pharmaceutical. T. Matsumoto: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co, Ltd, Bayer Co, Ltd, Bristol Myers Squibb Co, Ltd, Daiichi Sankyo Co, Ltd, Eli Lilly Japan Co, Ltd, Merck Bio Pharma Co, Ltd, MSD Co, Ltd, Taiho Pharmaceutical Co, Ltd, Takeda Co, Ltd. K. Yoshimura: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharma, MSD; Financial Interests, Personal, Advisory Board: Sysmex; Financial Interests, Personal, Writing Engagement: AstraZeneca. K. Muro: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Ono, Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly, Ono, Daiichi Sankyo, Taiho, Bristol Myers Squibb, Takeda; Financial Interests, Institutional, Research Grant, Including local PI as role: Astellas, Amgen, Sanofi, Daiichi Sankyo, Taiho, MSD, Pfizer, Merck Biopharma, Eisai, Ono, Novartis; Financial Interests, Personal, Steering Committee Member: Chugai, AstraZeneca, Amgen; Non-Financial Interests, Personal, Principal Investigator: Takeda. All other authors have declared no conflicts of interest.