Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial
Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial
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DOI：
10.1093/annonc/mdz402
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发表时间：
2019-12-01
影响因子：
50.5
通讯作者：
Furuse, J.
中科院分区：
文献类型：
--
作者：
Morizane, C.;Okusaka, T.;Furuse, J.
背景：吉西他滨联合顺铂(GC)是晚期胆道癌(BTC)的标准治疗方案，但它会引起恶心、呕吐和厌食，并需要补充水分。据报道，吉西他滨加S-1(GS)具有相同或更好的疗效和可接受的毒性。我们的目的是从总体生存期(OS)的角度来确认GS与GC在晚期/复发BTC患者中的非劣势。患者和方法：我们在日本的33家机构中进行了第三阶段的随机试验。资格标准包括化疗初期复发或无法切除的BTC患者，东部合作肿瘤组的表现状态为0-1，以及器官功能良好。计算的样本量为350，单侧a值为5%，方差为80%，非劣势边际风险比(HR)为1.155。主要终点是OS，次要终点包括无进展生存期(PFS)、有效率(RR)、不良事件(AEs)和临床显著不良事件(AEs)，定义为疲劳、厌食、恶心、呕吐、口腔粘膜炎或腹泻。结果：2013年5月至2016年3月，354名患者入选。GS不比GC差[中位数OS：GC 13.4个月，GS 15.1月，HR 0.945；90%可信区间0.78~1.15；非劣势P=0.046]。中位PFS：GC组为5.8个月，GS组为6.8个月(HR 0.86；95%CI 0.70~1.07)。GC组有效率为32.4%，GS组有效率为29.8%。这两种疗法总体上耐受性都很好。有临床意义的不良反应发生在GC组和GS组分别为35.1%和29.9%。结论：GS不需要补充水分，应考虑作为晚期/复发BTC患者的一种新的、方便的治疗方案。
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-naive 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 a 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.