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Association between homologous recombination gene variants and efficacy of oxaliplatin-based chemotherapy in advanced pancreatic cancer: prospective multicenter observational study

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Abstract

Next-generation sequencing (NGS)-based gene profiling can identify patients with pancreatic cancer with homologous recombinant repair gene pathogenic variants (HRRv). Several retrospective studies have reported a positive association between HRRv and the efficacy of platinum-based chemotherapy. However, this association remains to be validated in a prospective study. This multicenter, prospective, observational study included patients with histologically confirmed unresectable or recurrent pancreatic cancer who required systemic chemotherapy. Patients who were oxaliplatin-naïve patients were eligible. The HRRv status was measured using a College of American Pathologists-accredited NGS panel. One-year overall survival rate (1yr-OS%) was calculated after initiation of oxaliplatin-based chemotherapy and was set as the primary endpoint. Forty patients were enrolled between August 2018 and March 2020. The NGS success rate was 95% (38/40). HRRv was detected in 11 patients (27.5%). Oxaliplatin-based chemotherapy was administered to 9 of 11 patients with HRRv (81.8%) and 15 of 29 patients with non-HRRv (51.7%). The 1yr-OS% after initiation of oxaliplatin-based chemotherapy was 44.4% [95% confidence interval (CI) 13.7–71.9] and 57.1% (95% CI 28.4–78.0) in HRRv-positive and -negative cohorts, respectively. These data suggested that HRRv status alone could not be a potential predictive marker of oxaliplatin-based chemotherapy in patients with advanced pancreatic cancer. These results were in line with the results of a recent phase II study reporting the limited efficacy of poly(adenosine diphosphate–ribose) polymerase inhibitor in patients with pancreatic cancer who harbored HRRv other than BRCA. Future studies investigating patients with biallelic HRRv in the first-line setting are warranted.

Trial registration UMIN000033655.

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Data availability

Clinical data of patients in our study are not available for data sharing.

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Acknowledgements

The authors would like to thank the patients for their kind cooperation and Junko Suga, Kanami Ashida, Kumi Mukai, Haruna Mori, and Yuki Furuya for their excellent technical assistance and secretarial help. We also would like to thank Yi-Hua Jan, PhD (ACTgenomics) for the support in writing the Methods section. We are also grateful to Asuka Mizushima and other staff of the data center (Medical Research Support).

Funding

This research was supported by a Grant-in-Aid for Scientific Research C (17K08413) from the Japan Society for the Promotion of Science and by the Japan Agency for Medical Research and Development, AMED, under Grant number 17kk0305006h0001.

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Author notes

  1. Takahiro Yamada

    Present address: Division of Clinical Genetics, Hokkaido University Hospital, Hokkaido, Japan

Authors and Affiliations

  1. Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan

    Tomohiro Kondo, Masashi Kanai, Junichi Matsubara, Motoo Nomura, Taro Funakoshi, Akira Yokoyama, Keitaro Doi, Masashi Tamaoki, Shigemi Matsumoto & Manabu Muto

  2. Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan

    Tomohiro Kondo

  3. Department of Medical Oncology, Kyoto-Katsura Hospital, Kyoto, Japan

    Daisuke Yamaguchi

  4. Department of Clinical Oncology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

    Takashi Ura

  5. Department of Gastroenterology and Hepatology, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan

    Tadayuki Kou

  6. Department of Gastroenterology, Kobe City Nishi-Kobe Medical Center, Hyogo, Japan

    Toshinao Itani

  7. Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Michio Yoshimura

  8. Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Norimitsu Uza

  9. Clinical Genetics Unit, Kyoto University Hospital, Kyoto, Japan

    Takahiro Yamada

  10. Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Toshihiko Masui

  11. Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan

    Sachiko Minamiguchi

  12. Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Hideki Ishikawa

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  1. Tomohiro Kondo
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Corresponding author

Correspondence to Masashi Kanai.

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Conflict of interest

Masashi Kanai own stocks in Therabiopharma and received honoraria from Chugai Pharmaceutical Co., Ltd. Taro Funakoshi belongs to an endowed chair sponsored partly by Yakult Honsha Co., Ltd. and Chugai Pharmaceutical Co., Ltd. Manabu Muto received research funding and honoraria from Chugai Pharmaceutical Co., Ltd. All remaining authors have no conflict of interest to declare.

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Kondo, T., Kanai, M., Matsubara, J. et al. Association between homologous recombination gene variants and efficacy of oxaliplatin-based chemotherapy in advanced pancreatic cancer: prospective multicenter observational study. Med Oncol 40, 144 (2023). https://doi.org/10.1007/s12032-023-02011-y

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