Background: This open-label phase III trial evaluated efficacy and safety of S-1 plus cisplatin vs. cisplatin alone as first-line chemotherapy in patients with stage IVB, recurrent, or persistent cervical cancer. Methods: Patients were randomised (1:1) to S-1 plus cisplatin (study group) or cisplatin alone (control group). In each cycle, cisplatin 50 mg/m2 was administered on Day 1 in both groups. S-1 was administered orally at 80–120 mg daily on Days 1–14 of a 21-day cycle in the study group. The primary endpoint was overall survival (OS). Results: A total of 375 patients were enrolled, of whom 364 (188, study group; 176, control group) received treatment. Median OS was 21.9 and 19.5 months in the study and control groups, respectively (log-rank P = 0.125; hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.67–1.05). Median progression-free survival (PFS) was 7.3 and 4.9 months in the study and control groups, respectively (HR 0.62, 95% CI 0.48–0.80, P < 0.001). The adverse event (AE) rate increased in the study group despite the absence of any unexpected AEs. Conclusions: S-1 plus cisplatin did not show superiority over cisplatin alone in OS but significantly increased PFS in patients with stage IVB, recurrent, or persistent cervical cancer. Since the standard therapy has changed in the course of this study, further studies are warranted to confirm the clinical positioning of S-1 combined with cisplatin for this population.
Bibliographical noteFunding Information:
We thank all the patients, their families, and the investigators who participated in this study. We thank all the members of the independent data monitoring committee: Yutaka Ariyoshi (Aichi Cancer Center Aichi Hospital), Hiroyuki Yoshikawa (Ibaraki Prefectural Central Hospital), and Junzo Kigawa (Matsue City Hospital) for their contribution, and Kentaro Tsuji (Taiho Pharmaceutical Co., Ltd.) for his support in compiling and writing this report. This study was collaborated with the Japanese Gynecologic Oncology Group. Medical writing assistance was provided by Chiaki Fukuhara, Ph.D., and ASCA Corp, and funded by Taiho Pharmaceutical Co., Ltd. There is no applicable grant number.
Funding: This work was supported by Taiho Pharmaceutical Co., Ltd.
Competing interests: Y.A. has received research funding from Taiho. K.O. has served as a consultant for Taiho and Zeria. S.L. has received travel expense from Taiho. D.A. has received honoraria and research funding from Taiho. N.K. has received honoraria from Taiho, Sawai, Pfizer, Kyowa Hakko Kirin, Ono, Eisai, Takeda, Chugai, Nippon Kayaku, GlaxoSmithKline, Shionogi, Daiichi Sankyo, Yakult, Astellas, and Mochida. Y.H. has received honoraria from Taiho. K.F. has received honoraria from Kyowa Hakko Kirin, Zeria, Nippon Kayaku, Chugai, Eisai, Taiho, Yakult Honsha, Janssen Oncology, Daiichi Sankyo, Novartis, Eli Lilly Japan, Asahi Kasei, and Ono; has served as a consultant for Chugai, AstraZeneca, MSD, Pfizer, Taiho, and Eisai; and has received research funding from Eisai, GlaxoSmithKline, Taiho, Pfizer, Kaken, Chugai, Shionogi, Immunogen, Oncotherapeutics, AstraZeneca, Eli Lilly, Zeria, Ono, and MSD. M.T. has served as a consultant for AstraZeneca, Hisamitsu, AbbVie, Kyorin, Sanofi, Kowa, Taiho, Takeda, and Mitsubishi Tanabe. The remaining authors declare no competing interests.
All Science Journal Classification (ASJC) codes
- Cancer Research