Background Combination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment of metastatic colorectal cancer (mCRC). We carried out a randomized, open-label, phase III trial to determine whether S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS). Patients and methods Patients from 53 institutions who had previously untreated mCRC were randomly assigned (1 : 1) to receive either mFOLFOX6 or CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; a 3-week regimen: intravenous infusions of irinotecan 150 mg/m2 and bevacizumab 7.5 mg/kg on day 1, oral S-1 80 mg/m2 twice daily for 2 weeks, followed by a 1-week rest; or a 4-week regimen: irinotecan 100 mg/m2 and bevacizumab 5 mg/kg on days 1 and 15, S-1 80 mg/m2 twice daily for 2 weeks, followed by a 2-week rest). The primary end point was PFS. The noninferiority margin was 1.25; noninferiority would be established if the upper limit of the 95% confidence interval (CI) for the hazard ratio (HR) of the control group versus the experimental group was less than this margin. Result Between June 2012 and September 2014, 487 patients underwent randomization. Two hundred and forty-three patients assigned to the control group and 241 assigned to the experimental group were included in the primary analysis. Median PFS was 10.8 months (95% CI 9.6-11.6) in the control group and 14.0 months (95% CI 12.4-15.5) in the experimental group (HR 0.84, 95% CI 0.70-1.02; P < 0.0001 for noninferiority, P = 0.0815 for superiority). One hundred and fifty-seven patients (64.9%) in the control group and 140 (58.6%) in the experimental group had adverse events of grade 3 or higher. Conclusion S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment of mCRC and could be a new standard treatment. Clinical trials number UMIN000007834.

中文翻译：

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S-1和伊立替康联合贝伐单抗与mFOLFOX6或CapeOX联合贝伐单抗作为转移性结直肠癌患者的一线治疗（TRICOLORE）：一项随机，开放标签的III期非劣效性试验。

背景技术口服氟嘧啶和伊立替康的联合治疗尚未确立为转移性结直肠癌（mCRC）的一线治疗。我们进行了一项随机，开放标签的III期试验，以确定在无进展生存期（PFS）方面，S-1和伊立替康加贝伐单抗是否不劣于mFOLFOX6或CapeOX加贝伐单抗。患者和方法将53例先前未接受过mCRC治疗的机构的患者随机分配（1：1）接受mFOLFOX6或CapeOX加贝伐单抗（对照组）或S-1和伊立替康加贝伐单抗（实验组； 3周疗程：第1天静脉注射伊立替康150 mg / m2和贝伐单抗7.5 mg / kg，口服S-1 80 mg / m2，每天两次，持续2周，然后休息1周；或4周方案：在第1天和第15天，伊立替康100 mg / m2和贝伐单抗5 mg / kg，在第1天和第15天，S-1 80 mg / m2，每天两次，持续2周，然后休息2周。主要终点是PFS。非劣质性余量为1.25；如果对照组与实验组的危险比（HR）的95％置信区间（CI）的上限小于该范围，则将建立非劣效性。结果在2012年6月至2014年9月之间，对487例患者进行了随机分组。纳入分析的243名患者为对照组，有241名患者为实验组。对照组的中位PFS为10.8个月（95％CI 9.6-11.6），实验组为14.0个月（95％CI 12.4-15.5）（HR 0.84,95％CI 0.70-1.02;非劣效性P <0.0001 = 0.0815）。对照组157例（64.9％），实验组140例（58.6％）发生3级或更高的不良反应。结论S-1和伊立替康加贝伐单抗在作为mCRC的一线治疗的PFS方面不逊于mFOLFOX6或CapeOX加贝伐单抗。临床试验编号为UMIN000007834。