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Phase II clinical trial of gemcitabine plus oxaliplatin in patients with metastatic pancreatic adenocarcinoma with a family history of pancreatic/breast/ovarian/prostate cancer or personal history of breast/ovarian/prostate cancer (FABRIC study)

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Abstract

Background

A family/personal history of breast, ovarian, or pancreatic cancer is a useful predictive marker for response to platinum-based chemotherapy in treating patients with pancreatic cancer. These cancers, and prostate cancer, are known as BRCA-related malignancies. We evaluated the efficacy of gemcitabine plus oxaliplatin (GEMOX) in patients with metastatic pancreatic cancer with a family/personal history of these cancers.

Methods

Chemotherapy-naïve patients with metastatic pancreatic cancer with a family history of pancreatic/breast/ovarian/prostate cancer or a personal history of breast/ovarian/prostate cancer were included. Patients received fixed dose-rate gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2) every 2 weeks. The primary endpoint was 1-year survival, and the threshold and expected values were set at 30 and 50%, respectively. The target sample size was determined to be 43, with a one-sided alpha value of 5% and power of 80%. A total of 45 patients were enrolled.

Results

Among the first 43 enrolled patients, the 1-year survival rate was 27.9% [90% confidence interval (CI) 17.0–41.3], which did not meet the primary endpoint. Median overall survival, progression-free survival, and response rates were 7.6 months (95% CI 6.0–10.7), 4.0 months (95% CI 2.0–4.6), and 26.7% (95% CI 14.6–41.9), respectively, in all registered patients. The GEMOX regimen was generally tolerated; the most common grade three or higher adverse events were hematological toxicities.

Conclusion

GEMOX did not show the expected efficacy in patients with metastatic pancreatic cancer with a family or personal history of pancreatic/breast/ovarian/prostate cancer. Selection of GEMOX based on family/personal history is not recommended.

Trial registration number

UMIN000017894.

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Acknowledgements

We wish to thank all the patients and their families for participating in this study. We are grateful to all the investigators in this trial. This research was partially supported by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and development, AMED.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan

    Naohiro Okano & Junji Furuse

  2. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan

    Chigusa Morizane & Takuji Okusaka

  3. Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Kashiwa, Japan

    Shogo Nomura

  4. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Hideaki Takahashi & Masafumi Ikeda

  5. Department of Gastroenterology, Hyogo Cancer Center, Hyogo, Japan

    Hidetaka Tsumura

  6. Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan

    Hironaga Satake

  7. Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan

    Nobumasa Mizuno

  8. Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan

    Kunihiro Tsuji

  9. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan

    Kazuhiko Shioji

  10. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan

    Akinori Asagi

  11. Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Kohichiroh Yasui

  12. Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo, Japan

    Sho Kitagawa

  13. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan

    Tomomi Kashiwada

  14. Department of Medical Oncology, Teine Keijinkai Hospital, Sapporo, Japan

    Atsushi Ishiguro

  15. Department of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Masashi Kanai

  16. Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan

    Makoto Ueno

  17. Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan

    Takashi Ogura

  18. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan

    Satoshi Shimizu

  19. Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    Kazutoshi Tobimatsu

  20. Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Masayo Motoya

  21. Department of Clinical Oncology, University of Miyazaki Hospital, Miyazaki, Japan

    Koji Nakashima

Authors
  1. Naohiro Okano
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  2. Chigusa Morizane
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  3. Shogo Nomura
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  4. Hideaki Takahashi
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  5. Hidetaka Tsumura
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  6. Hironaga Satake
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  7. Nobumasa Mizuno
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  8. Kunihiro Tsuji
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  9. Kazuhiko Shioji
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  10. Akinori Asagi
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  11. Kohichiroh Yasui
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  12. Sho Kitagawa
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  13. Tomomi Kashiwada
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  15. Masashi Kanai
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  16. Makoto Ueno
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  17. Takashi Ogura
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  18. Satoshi Shimizu
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  19. Kazutoshi Tobimatsu
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  20. Masayo Motoya
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  21. Koji Nakashima
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  22. Masafumi Ikeda
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  23. Takuji Okusaka
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  24. Junji Furuse
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Contributions

All authors contributed to the study conception and design. Provision of material or patients, data collection and analysis were performed by all authors. The first draft of the manuscript was written by NO, CM, SN, and JF and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Naohiro Okano.

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Conflict of interest

Morizane C. received research funding from Yakult Honsha, and Eli Lilly Japan. Satake H. received honoraria from Eli Lilly Japan. Mizuno N. received research funding from Dainippon Sumitomo Pharma, MSD, ASLAN Pharmaceuticals, Incyte, and Yakult Honsha. Kanai M received from honoraria from Chugai Pharmaceutical. Shimizu S. received research funding from Yakult Honsha.Ikeda M. received honoraria from Eli Lilly Japan, and received research funding from Yakult Honsha. Okusaka T. received research funding from AstraZeneca, Chugai Pharmaceutical, Eisai, Novartis Pharma, and Bristol-Myers. Furuse J. received honoraria and research funding from Yakult Honsha, and Eli Lilly Japan. The other authors declare that they have no conflict of interest.

Ethical approval

The study was performed in accordance with the ethical standards established in the 1964 Declaration of Helsinki and its later amendments. The study was approved by the institutional review board of each study site, and all the patients provided informed consent prior to their inclusion in the study.

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Okano, N., Morizane, C., Nomura, S. et al. Phase II clinical trial of gemcitabine plus oxaliplatin in patients with metastatic pancreatic adenocarcinoma with a family history of pancreatic/breast/ovarian/prostate cancer or personal history of breast/ovarian/prostate cancer (FABRIC study). Int J Clin Oncol 25, 1835–1843 (2020). https://doi.org/10.1007/s10147-020-01721-x

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