Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: The FUGA-BT (JCOG1113) Randomized Phase III Clinical Trial
Mené sur 354 patients atteints d'un cancer des voies biliaires de stade avancé ou récidivant, cet essai de phase III évalue la non infériorité, du point de vue de la survie globale, et la toxicité d'un traitement combinant gemcitabine et S-1 par rapport à un traitement combinant gemcitabine et cisplatine
Background : Gemcitabine plus cisplatin (GC) is the standard treatment for 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 1-sided alpha of 5%, a power of 80%, and non-inferiority margin hazard ratio of 1.155. The primary endpoint was OS, while the secondary endpoints 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, hazard ratio [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.
Annals of Oncology 2019