Junzo Hamanishi1, Nobuhiro Takeshima2,3, Noriyuki Katsumata4, Kimio Ushijima5, Tadashi Kimura6, Satoshi Takeuchi7,8, Koji Matsumoto9, Kimihiko Ito10, Masaki Mandai11,12, Hidekatsu Nakai11, Noriaki Sakuragi13,14, Hidemichi Watari13, Nobutaka Takahashi15, Hidenori Kato16, Kosei Hasegawa17, Kan Yonemori18, Mika Mizuno19,20, Kazuhiro Takehara21, Hitoshi Niikura22,23, Takashi Sawasaki24,25, Sari Nakao26, Toshiaki Saito27, Takayuki Enomoto28, Satoru Nagase29, Nao Suzuki30, Takashi Matsumoto31, Eiji Kondo32, Kenzo Sonoda33,34, Satomi Aihara35,36, Yoichi Aoki37, Aikou Okamoto38, Hirokuni Takano39, Hiroshi Kobayashi40,41, Hisamori Kato42, Yoshito Terai43,44, Akira Takazawa45, Yusuke Takahashi46, Yoshinobu Namba47, Daisuke Aoki48, Keiichi Fujiwara17, Toru Sugiyama7,49, Ikuo Konishi50. 1. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 2. Department of Gynecology, Cancer Institute Hospital of JFCR, Tokyo, Japan. 3. Current affiliation: Department of Obstetrics and Gynecology, International University of Health and Welfare Hospital, Otawara, Japan. 4. Department of Medical Oncology, Nippon Medical School Musashikosugi Hospital, Kawasaki, Japan. 5. Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan. 6. Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan. 7. Department of Obstetrics and Gynecology, Iwate Medical University Hospital, Iwate, Japan. 8. Current affiliation: Department of Gynecology, Kobe Tokushukai Hospital, Kobe, Japan. 9. Department of Medical Oncology, Hyogo Cancer Center, Akashi, Japan. 10. Department of Obstetrics and Gynecology, Kansai Rosai Hospital, Amagasaki, Japan. 11. Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osakasayama, Japan. 12. Current affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 13. Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 14. Current affiliation: Department of Gynecology, Otaru General Hospital, Otaru, Japan. 15. Division of Gynecology, Shizuoka Cancer Center, Shizuoka, Japan. 16. Department of Gynecology, Hokkaido Cancer Center, Sapporo, Japan. 17. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan. 18. Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 19. Department of Obstetrics and Gynecology, Aichi Cancer Center Hospital, Nagoya, Japan. 20. Current affiliation: Department of Obstetrics and Gynecology, Kagoshima University Hospital, Kagoshima, Japan. 21. Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 22. Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan. 23. Current affiliation: Department of Obstetrics and Gynecology, National Hospital Organization Sendai Medical Center, Sendai, Japan. 24. Department of Obstetrics and Gynecology, National Hospital Organization Kure Medical Center, Kure, Japan. 25. Current affiliation: SAWASAKI Obstetrics Gynecology Clinic, Kure, Japan. 26. Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba Hospital, Tsukuba, Japan. 27. Gynecology Service, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 28. Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 29. Department of Obstetrics and Gynecology, Yamagata University Hospital, Yamagata, Japan. 30. Department of Obstetrics and Gynecology, St Marianna University School of Medicine, Kawasaki, Japan. 31. Department of Obstetrics and Gynecology, Ehime University Hospital, Toon, Japan. 32. Department of Obstetrics and Gynecology, Mie University Hospital, Tsu, Japan. 33. Department of Obstetrics and Gynecology, Kyushu University Hospital, Fukuoka, Japan. 34. Current affiliation: Department of Gynecologic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 35. Department of Obstetrics and Gynecology, Faculty of Medicine, Saga University Hospital, Saga, Japan. 36. Current affiliation: Department of Medical Oncology, Eguchi Hospital, Saga, Japan. 37. Department of Obstetrics and Gynecology, University of the Ryukyus Hospital, Okinawa, Japan. 38. Department of Obstetrics and Gynecology, The Jikei University Hospital, Tokyo, Japan. 39. Department of Obstetrics and Gynecology, The Jikei University Kashiwa Hospital, Kashiwa, Japan. 40. Department of Obstetrics and Gynecology, Nara Medical University Hospital, Kashihara, Japan. 41. Current affiliation: Ms Clinic MayOne, Kashihara, Japan. 42. Department of Gynecology, Kanagawa Cancer Center, Yokohama, Japan. 43. Department of Gynecologic Oncology, Osaka Medical College Hospital, Takatsuki, Japan. 44. Current affiliation: Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan. 45. Data Science, Ono Pharmaceutical Co, Ltd, Osaka, Japan. 46. Oncology Clinical Development Unit, Ono Pharmaceutical Co, Ltd, Osaka, Japan. 47. Clinical Science, Ono Pharmaceutical Co, Ltd, Osaka, Japan. 48. Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan. 49. Current affiliation: Department of Obstetrics and Gynecology, St Mary's Hospital, Kurume, Japan. 50. National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
Abstract
PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.
PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.
Authors: Dmitriy Zamarin; Robert A Burger; Michael W Sill; Daniel J Powell; Heather A Lankes; Michael D Feldman; Oliver Zivanovic; Camille Gunderson; Emily Ko; Cara Mathews; Sudarshan Sharma; Andrea R Hagemann; Samir Khleif; Carol Aghajanian Journal: J Clin Oncol Date: 2020-04-10 Impact factor: 44.544
Authors: Suzanne L Topalian; F Stephen Hodi; Julie R Brahmer; Scott N Gettinger; David C Smith; David F McDermott; John D Powderly; Richard D Carvajal; Jeffrey A Sosman; Michael B Atkins; Philip D Leming; David R Spigel; Scott J Antonia; Leora Horn; Charles G Drake; Drew M Pardoll; Lieping Chen; William H Sharfman; Robert A Anders; Janis M Taube; Tracee L McMiller; Haiying Xu; Alan J Korman; Maria Jure-Kunkel; Shruti Agrawal; Daniel McDonald; Georgia D Kollia; Ashok Gupta; Jon M Wigginton; Mario Sznol Journal: N Engl J Med Date: 2012-06-02 Impact factor: 91.245
Authors: Christian Kurzeder; Isabel Bover; Frederik Marmé; Joern Rau; Patricia Pautier; Nicoletta Colombo; Domenica Lorusso; Petronella Ottevanger; Maria Bjurberg; Christian Marth; Pilar Barretina-Ginesta; Ignace Vergote; Anne Floquet; Josep M Del Campo; Sven Mahner; Lydie Bastière-Truchot; Nicolas Martin; Mikkel Z Oestergaard; Astrid Kiermaier; Carmen Schade-Brittinger; Sandra Polleis; Andreas du Bois; Antonio Gonzalez-Martin Journal: J Clin Oncol Date: 2016-06-06 Impact factor: 44.544
Authors: Razvan Cristescu; Robin Mogg; Mark Ayers; Andrew Albright; Erin Murphy; Jennifer Yearley; Xinwei Sher; Xiao Qiao Liu; Hongchao Lu; Michael Nebozhyn; Chunsheng Zhang; Jared K Lunceford; Andrew Joe; Jonathan Cheng; Andrea L Webber; Nageatte Ibrahim; Elizabeth R Plimack; Patrick A Ott; Tanguy Y Seiwert; Antoni Ribas; Terrill K McClanahan; Joanne E Tomassini; Andrey Loboda; David Kaufman Journal: Science Date: 2018-10-12 Impact factor: 47.728
Authors: David G Mutch; Mauro Orlando; Tiana Goss; Michael G Teneriello; Alan N Gordon; Scott D McMeekin; Yanping Wang; Dennis R Scribner; Martin Marciniack; R Wendel Naumann; Angeles Alvarez Secord Journal: J Clin Oncol Date: 2007-07-01 Impact factor: 44.544
Authors: Ignace Vergote; Antonio Gonzalez-Martin; Domenica Lorusso; Charlie Gourley; Mansoor Raza Mirza; Jean-Emmanuel Kurtz; Aikou Okamoto; Kathleen Moore; Frédéric Kridelka; Iain McNeish; Alexander Reuss; Bénédicte Votan; Andreas du Bois; Sven Mahner; Isabelle Ray-Coquard; Elise C Kohn; Jonathan S Berek; David S P Tan; Nicoletta Colombo; Rongyu Zang; Nicole Concin; Dearbhaile O'Donnell; Alejandro Rauh-Hain; C Simon Herrington; Christian Marth; Andres Poveda; Keiichi Fujiwara; Gavin C E Stuart; Amit M Oza; Michael A Bookman Journal: Lancet Oncol Date: 2022-08 Impact factor: 54.433
Authors: Jason A Konner; Dmitriy Zamarin; Tiffany Y Sia; Beryl Manning-Geist; Sushmita Gordhandas; Rajmohan Murali; Antonio Marra; Ying L Liu; Claire F Friedman; Travis J Hollmann; Oliver Zivanovic; Dennis S Chi; Britta Weigelt Journal: Int J Gynecol Cancer Date: 2022-08-01 Impact factor: 4.661