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Poster session 21

1561P - APC mutation (mt.), MYC, and GATA6 amplifications (amp.) were associated with worse survival in HER2-positive advanced gastric cancer patients treated with S-1/capecitabine plus oxaliplatin combined with trastuzumab (T-mab) and nivolumab (N-mab)

Date

21 Oct 2023

Session

Poster session 21

Topics

Tumour Immunology;  Translational Research;  Targeted Therapy

Tumour Site

Gastric Cancer

Presenters

Takeru Wakatsuki

Citation

Annals of Oncology (2023) 34 (suppl_2): S852-S886. 10.1016/S0923-7534(23)01930-0

Authors

T. Wakatsuki1, D. Takahari1, N. Yamamoto2, A. Ooki1, K. Chin1, N. Kurihara3, T. Mashima4, M. Ogura1, I. Nakayama1, S. Fukuoka1, H. Hirano5, K. Minashi6, H. Hara7, K. Kato8, N. Ishizuka3, S. Kitano9, H. Seimiya4, K. Takeuchi2, N. Boku10, K. Yamaguchi1

Author affiliations

  • 1 Gastrointestinal Medical Oncology, The Cancer Institute Hospital of JFCR, 1358550 - Koto-ku/JP
  • 2 Pathology, The Cancer Institute Hospital of JFCR, 1358550 - Koto-ku/JP
  • 3 Clinical Planning And Strategy, The Cancer Institute Hospital of JFCR, 1358550 - Koto-ku/JP
  • 4 Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1358550 - Koto-ku/JP
  • 5 Gastrointestinal Medical Oncology Division, NCCH - National Cancer Center Hospital-Tsukiji Campus, 104-0045 - Chuo-ku/JP
  • 6 Clinical Trial Promotion Department, Chiba Cancer Center Hospital, 260-8717 - Chiba/JP
  • 7 Gastroenterology, Saitama Cancer Center, 362-0806 - Ina/JP
  • 8 Department Of Gastrointestinal Medical Oncology, National Cancer Center - Tsukiji Campus, 104-0045 - Chuo-ku/JP
  • 9 Advanced Medical Development, The Cancer Institute Hospital of JFCR, 1358550 - Koto-ku/JP
  • 10 Department Of Onology And General Medicine, IMS Hospital, Institute of Medical Science, University of Tokyo, 1358550 - Minato-ku/JP

Resources

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Abstract 1561P

Background

Recently, we reported safety and efficacy of T-mab plus N-mab with S-1/Capecitabine plus oxaliplatin (UMIN000034222). The aim of this study was to explore a candidate biomarker for this new combination therapy.

Methods

Patients were treated with S-1 80 mg/m2/day or Capecitabine 2000 mg/m2/day on days 1-14 with oxaliplatin 130 mg/m2, N-mab 360mg, and T-mab 8mg/kg for initial treatment, and subsequently with 6 mg/kg on day 1, repeated every 3 weeks. Pre-treatment primary tumor samples were collected for whole exome sequencing (WES).

Results

42 patients enrolled in this clinical trial, and WES was performed on 23 patients. In the copy number analysis, ERBB2 amp. was observed most frequently in 15 patients (65%). Subsequently, GATA6, MYC and CCNE1 amp. were observed in 8 (35%), 6 (26%), and 5 (22%) patients, respectively. In the mutation analysis, TP53 was observed most frequently in 20 patients (87%). Subsequently, mutations in APC, ERBB3, and PIK3CA were observed in 6 (26%), 3 (13%), and 3 (13%) patients, respectively. Among them, APC mut., MYC, and GATA6 amp. were associated with worse survival. Patients with APC mut. showed significantly shorter PFS (median 5.6 vs 20.8 months, HR 3.47, 95%CI 1.16-10.44, p = 0.018), but not for OS (median 21.0 vs 26.5 months, HR 1.19, 95%CI 0.31-4.60, p = 0.806). Patients with MYC amp. showed significantly shorter PFS (median 4.2 vs 18.0 months, HR 3.48, 95%CI 1.09-11.12, p = 0.024) and OS (median 13.9 months vs not reached, HR 3.97, 95%CI 0.95-16.54, p = 0.042), respectively. Patients with GATA6 amp. showed significantly shorter PFS (median 5.8 vs 32.0 months, HR 3.53, 95%CI 1.25-9.99, p = 0.011) and OS (median 13.9 months vs not reached, HR 3.74, 95%CI 1.04-13.40, p = 0.030). As for objective response rates (ORRs), patients with APC mut. and MYC amp. showed lower response rates (50% vs 82% for APC mut., 67% vs 77% for MYC amp.), whereas comparable ORR was shown for GATA6 amp. (75% vs 73 %).

Conclusions

APC mut., MYC, and GATA6 amp. may have negative clinical impacts on the effects of the new combination therapy including T-mab and N-mab.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Ono Pharmaceutical Co., Ltd.

Disclosure

K. Chin: Financial Interests, Personal, Speaker’s Bureau: Taiho Pharma, Ono Pharmaceutical Co.Ltd., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Merck & Co., Inc. K. Minashi: Financial Interests, Institutional, Research Grant: Amgen, Taiho, Daiichi Sankyo Co., Ltd, Astellas Pharmaceutical Co., Ltd,. H. Hara: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Boehringer Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, MSD, Ono, Bayer, Chugai, Lilly, Merck Biopharma, Taiho, Takeda, Yakult, Bristol Myers Squibb; Financial Interests, Institutional, Coordinating PI: Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Janssen, Merck Biopharma, MSD, Ono, Taiho, ALX oncology. K. Kato: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bristol Myers Squibb, Merck and Co; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical, Bristol Myers Squibb, Merck and Co, Bayer, AstraZeneca, BeiGene, Taiho, Merck Biophrma, Amgen, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Ono Pharmaceuticals, Merck & Co; Financial Interests, Institutional, Local PI: Bayer, AstraZeneca, BeiGene, Chugai, Taiho, Oncolys Biopharma, Janssen Pharmaceutical. N. Boku: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Eli Lilly, Ono Pharmaceutical, Taiho, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical, Ono Pharmaceutical. K. Yamaguchi: Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Bristol Myers Squibb, Ono, Eli Lilly Japan; Financial Interests, Institutional, Funding: Taiho. All other authors have declared no conflicts of interest.

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