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Nivolumab in patients with unresectable locally advanced or metastatic urothelial carcinoma: CheckMate 275 2-year global and Japanese patient population analyses

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Abstract

Background

Nivolumab has demonstrated antitumor activity and manageable safety in the single-arm, phase II CheckMate 275 study in patients with unresectable locally advanced or metastatic platinum-resistant urothelial carcinoma. We report updated results of the global population and a subanalysis of Japanese patients from this study.

Methods

Patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) confirmed by blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS) by BIRC and overall survival (OS). Safety was also reported. The minimum follow-up was 21 months.

Results

Overall, 270 patients were treated with nivolumab globally; 23 patients were Japanese. In the global and Japanese populations, respectively, ORR per BIRC was 20.4% and 21.7%; median PFS was 1.9 (95% confidence interval [CI] 1.9–2.3) and 3.8 months (95% CI 1.9–7.2); and median OS was 8.6 (95% CI 6.1–11.3) and 21.0 months (95% CI 7.2–not reached). The most common any grade treatment-related adverse events were fatigue (18.1%) and diarrhea (12.2%) in the global population; the most common in the Japanese population were diarrhea (26.1%) and pyrexia (13.0%). Grade 3 or 4 treatment-related adverse events occurred in 61 (22.6%) and seven (30.4%) of the global and Japanese patients, respectively.

Conclusions

Nivolumab continues to show antitumor activity and survival in the global population of CheckMate 275. Meaningful clinical benefit was also observed in Japanese patients. No new safety signals were identified.

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Acknowledgements

The authors thank the patients and their families, the investigators and participating study teams, and the Faculty of Medicine, University of Tokyo. Professional medical writing and editorial assistance were provided by Nicolette Belletier, Ph.D, and Lawrence Hargett of PAREXEL, funded by Bristol-Myers Squibb KK and ONO Pharmaceutical Co., Ltd.

Funding

This study was funded by Bristol-Myers Squibb and ONO Pharmaceutical Co., Ltd.

Author information

Authors and Affiliations

  1. Department of Urology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan

    Chikara Ohyama

  2. Department of Urology, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan

    Takahiro Kojima

  3. Department of Urology, Tokyo Women’s Medical University Medical Center East, 2-1-10 Nishiogu, Arakawa-ku, Tokyo, 116-8567, Japan

    Tsunenori Kondo

  4. Department of Urology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Hirokoji-agaru, Kawaramachi-dori, Kamigyo-ku, Kyoto, 602-8566, Japan

    Yoshio Naya

  5. Department of Urology, Meiji University of Integrative Medicine, Honoda, Hiyoshi-cho, Nantan, 629-0301, Japan

    Yoshio Naya

  6. Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan

    Takamitsu Inoue

  7. Department of Urology, Niigata University Graduate School of Medicine and Dental Sciences, 757 Ichibancho, Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan

    Yoshihiko Tomita

  8. Department of Urology, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

    Masatoshi Eto

  9. Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Masatoshi Eto

  10. Department of Urology, Chiba-Nishi General Hospital, Kanagasaku 107-1, Matsudo City, Chiba, 270-2251, Japan

    Shinichi Hisasue

  11. Department of Urology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan

    Hirotsugu Uemura

  12. Department of Urology, Iwate Medical University, 19-1 Uchimaru, Morioka, 020-8505, Japan

    Wataru Obara

  13. Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Eiji Kikuchi

  14. Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Padmanee Sharma & Arlene Siefker-Radtke

  15. Department of Hematology and Oncology, Mount Sinai Medical Center, 10 East 102nd Street, New York, NY, 10029, USA

    Matthew D. Galsky

  16. Bristol-Myers Squibb, 3401 Princeton Pike, Lawrence Township, NJ, 08648, USA

    Gary Grossfeld, Sandra Collette & Kyna Gooden

  17. Department of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan

    Go Kimura

Authors
  1. Chikara Ohyama
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  2. Takahiro Kojima
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  3. Tsunenori Kondo
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  4. Yoshio Naya
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  5. Takamitsu Inoue
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  6. Yoshihiko Tomita
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  7. Masatoshi Eto
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  8. Shinichi Hisasue
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  9. Hirotsugu Uemura
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  10. Wataru Obara
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  11. Eiji Kikuchi
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  12. Padmanee Sharma
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  13. Matthew D. Galsky
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  14. Arlene Siefker-Radtke
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  15. Gary Grossfeld
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  16. Sandra Collette
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  17. Kyna Gooden
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  18. Go Kimura
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Corresponding author

Correspondence to Chikara Ohyama.

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Conflict of interest

Chikara Ohyama, Takahiro Kojima, Yoshio Naya, Takamitsu Inoue, and Shinichi Hisasue declare having no conflict of interest. Tsunenori Kondo has received honoraria from ONO Pharmaceutical and Pfizer. Yoshihiko Tomita declares an advisory role for Novartis, Taiho Pharmaceutical, and ONO Pharmaceutical, received honoraria from Astellas, ONO Pharmaceutical, Pfizer, Sonafi Aventis, and Bristol-Myers Squibb, and received research funding from Astellas, AstraZeneca, Pfizer, and ONO Pharmaceutical. Masatoshi Eto received honoraria from ONO Pharmaceutical and Bristol-Myers Squibb, and research funding from ONO Pharmaceutical. Hirotsugu Uemura received honoraria from Bayer, AstraZeneca, Takeda, Astellas, Sanofi, Janssen, MSD, Bristol-Myers Squibb, and Pfizer, and received research funding from AstraZeneca, Janssen, Takeda, Astellas, Sanofi, Taiho, ONO Pharmaceutical, and Pfizer. Wataru Obara received honoraria from Bristol-Myers Squibb and research funding from Bristol-Myers Squibb. Eiji Kikuchi received honoraria from ONO Pharmaceutical, Kissei Pharmaceutical, ASKA Pharmaceutical, Nippon Shinyaku Taiho, Takeda, MSD, Pfizer, AstraZeneca, Astellas, and Chugai, and received research funding from MSD, Nippon Kayaku, Astellas, ONO Pharmaceutical, Chugai, Takeda, Taiho, and AstraZeneca. Padmanee Sharma owns stock in Jounce, Neon, Constellation, Oncolytics, BioAtla, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak, ImaginAb, and Hummingbird, reports an advisory role in Constellation, Jounce, Neon, BioAtla, Pieris, Oncolytics, Merck, Forty-Seven, Polaris, Apricity, Marker Therapeutics, Codiak, ImaginAb, Hummingbird, and owns a patent licensed to Jounce. Matthew D. Galsky received research funding from Bristol-Myers Squibb, Genentech, AstraZeneca, and Merck. Arlene Siefker-Radtke reports an advisory role for Nektar Therapeutics, Janssen Biotech, Bavarian Nordic, Merck Sharp and Dohme, and Seattle Genetics, and research funding from Janssen, Takeda, Nektar Therapeutics, and Bioclin. Gary Grossfeld reports employment at Bristol-Myers Squibb and owns stock in Bristol-Myers Squibb. Sandra Collette reports employment at Bristol-Myers Squibb. Kyna Gooden reports employment at Bristol-Myers Squibb and owns stock in Bristol-Myers Squibb. Go Kimura received honoraria from ONO Pharmaceutical, Bristol-Myers Squibb, Novartis, Bayer, and Chugai.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study

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Ohyama, C., Kojima, T., Kondo, T. et al. Nivolumab in patients with unresectable locally advanced or metastatic urothelial carcinoma: CheckMate 275 2-year global and Japanese patient population analyses. Int J Clin Oncol 24, 1089–1098 (2019). https://doi.org/10.1007/s10147-019-01450-w

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  • DOI: https://doi.org/10.1007/s10147-019-01450-w

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