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Poster session 21

1566P - Clinical relevance of circulating tumor DNA in HER2 -positive advanced gastric cancer: Results from phase Ib trial of HER2 and PD-1 dual targeted therapy (Ni-High)

Date

21 Oct 2023

Session

Poster session 21

Topics

Clinical Research;  Targeted Therapy;  Genetic and Genomic Testing;  Immunotherapy

Tumour Site

Gastric Cancer

Presenters

Hiroki Osumi

Citation

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

Authors

H. Osumi1, T. Wakatsuki1, D. Takahari1, A. Ooki1, K. Chin1, H. Shoji2, M. Ogura1, I. Nakayama1, N. Yamamoto3, H. Hirano2, H. Hara4, K. Minashi5, E. Shinozaki1, K. Kato2, N. Kurihara6, S. Kitano7, K. Takeuchi3, N. Boku8, K. Yamaguchi1

Author affiliations

  • 1 Department Of Gastroenterological Chemotherapy, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Tokyo/JP
  • 2 Department Of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 3 Department Of Pathology, The Cancer Institute Hospital of JFCR, 1358550 - Koto-ku/JP
  • 4 Department Of Gastroenterology, Saitama Cancer Center, 362-0806 - Saitama/JP
  • 5 Clinical Trial Promotion Department, Chiba Cancer Center Hospital, 260-8717 - Chiba/JP
  • 6 Clinical Planning And Strategy, The Cancer Institute Hospital of JFCR, 1358550 - Koto-ku/JP
  • 7 Department Of Advanced Medical Development, Divisions Of Cancer Immunotherapy Development And Clinical Chemotherapy, Japanese Foundation for Cancer Research, 135-8550 - Koto-ku/JP
  • 8 Department Of Onology And General Medicine, IMS Hospital, Institute of Medical Science, University of Tokyo, 108-8639 - Tokyo/JP

Resources

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Abstract 1566P

Background

Anti-PD-1 antibody in addition to HER2-targeted therapy and chemotherapy may enhance antibody-dependent cell-mediated cytotoxicity and add further chemotherapeutic efficacy for HER2 -positive advanced gastric cancer (AGC). On the other hand, it remains unclear molecular profiles related to efficacy and resistance to this dual targeted therapy. Real-time tracking of these changes of the alteration using ctDNA may contribute to the treatment optimization.

Methods

We enrolled tissue-confirmed HER2 -positive AGC who received chemotherapy with HER2 and anti-PD-1 dual targeted therapy from phase Ib clinical trial. Genomic profiling of 74 genes of their plasma by next-generation sequencing was carried out using ctDNA panel (Guardant 360®) to compare with their clinical parameters, clinical outcomes of dual targeted therapy and HER2 gene amplifications in matched tissue samples.

Results

Twenty-one patients were eligible in this study. HER2 gene amplification and single nucleotide variant (SNV) / Indels were detected in 12 (57.1%), 3 (14.3%) patients, respectively. Maximum mutant allele frequency (mMAF) in diffuse type histology were significantly lower than intestinal type histology (P = 0.01), and mMAF were associated with tumor diameter (r = 0.626, P = 0.0032). Tissue and ctDNA HER2 copy numbers were significantly correlated (r = 0.662, P = 0.019). Patients without HER2 SNV / Indels (n=17) had significantly longer PFS and OS than patients with HER2 SNV / Indels (n=3) (median PFS: 20.8 vs 8.4 months; P = 0.04; HR, 0.24, median OS: NA vs 14.0 months; P = 0.037; HR, 0.18). Moreover, patients with focal HER2 gene amplification (n = 9) had significantly longer PFS and OS than patients with HER2 aneuploidy (n=3) (median PFS: 20.8 vs 8.4 months; P = 0.007; HR, 0.08, median OS: NA vs 14.8 months; P = 0.0046; HR, 0.077). In patients achieving CR or PR (n=16), mMAF 3 weeks after initiation of chemotherapy was significantly lower than those in patients achieving SD (n=4) (P = 0.0087).

Conclusions

Our data confirmed that HER2 SNV / Indels and gene amplification status may be predictor of treatment efficacy in patients with HER2- positive AGC who received chemotherapy with HER2 and PD-1 dual targeted therapy.

Clinical trial identification

UMIN000034222.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Ono Pharamceutical Co., Ltd.

Disclosure

H. Shoji: Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co., Ltd., Zymeworks inc.; Financial Interests, Institutional, Local PI: Ono Pharmaceutical Co., Ltd., MSD, Astellas, Amgen, Daiichi Sankyo; Financial Interests, Institutional, Funding: Ono Pharmaceutical Co., Ltd., Takeda Pharmaceuticals. H. Hirano: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Ono Pharmaceutical, Teijin Pharma, 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, Incyte, BeiGene, Novartis. 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. Minashi: Financial Interests, Institutional, Research Grant: Amgen, Taiho, Daiichi Sankyo Co., Ltd, Astellas Pharmaceutical Co., Ltd,. 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 Pharm, Eli Lilly Japan; Financial Interests, Institutional, Funding: Taiho. All other authors have declared no conflicts of interest.

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