Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. (30th September 2019)

• Record Type: Journal Article
• Authors: Morizane, C; Okusaka, T; Mizusawa, J; Katayama, H; Ueno, M; Ikeda, M; Ozaka, M; Okano, N; Sugimori, K; Fukutomi, A; Hara, H; Mizuno, N; Yanagimoto, H; Wada, K; Tobimatsu, K; Yane, K; Nakamori, S; Yamaguchi, H; Asagi, A; Yukisawa, S; Kojima, Y; Kawabe, K; Kawamoto, Y; Sugimoto, R; Iwai, T; Nakamura, K; Miyakawa, H; Yamashita, T; Hosokawa, A; Ioka, T; Kato, N; Shioji, K; Shimizu, K; Nakagohri, T; Kamata, K; Ishii, H; Furuse, J;
• Is Part Of: Annals of oncology. Volume 30:Number 12(2019)
• Page Start: 1950
• Page End: 1958
• Publication Date: 2019-09-30
• Subjects: advanced biliary tract cancer -- first-line chemotherapy -- gemcitabine plus S-1 -- phase III randomized trial; Oncology -- Periodicals; 616.992
• DOI: 10.1093/annonc/mdz402
• Languages: English
• ISSNs: 0923-7534

Abstract

Abstract: Background: Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS). Patients and methods: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 − 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea. Results: Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78–1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70–1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm. Conclusions: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC. Clinical Trial number: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm ), number UMIN000010667.