For patients with surgically unresectable metastatic colorectal cancer, a continuum of care is offered to improve their overall outcome. Few treatment options exist apart from oxaliplatin and irinotecan-based therapies; even fewer exist for patients with RAS mutations, who account for 30–60% of all patients with metastatic colorectal cancer. When the oral agent, TAS-102, was approved by the US Food and Drug Administration in 2017, it offered another potential option for patients with surgically unresectable, metastatic colorectal cancer. Often incorrectly touted as a modified oral fluorouracil, TAS-102 differentiates itself by being comprised of two components: trifluridine, a nucleoside analogue, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor, combined in a 1·0:0·5 ratio. Tipiracil prevents rapid degradation of trifluridine resulting in increased bioavailability. The phase 3 RECOURSE trial randomly assigned patients (2:1) with metastatic colorectal cancer (n=800) to receive either TAS-102 (35 mg/m ², days 1–5 and 8–12) or placebo. The primary endpoint of overall survival was met, with longer median overall survival in the TAS-102 group (7·1 months vs 5·3 months in the placebo group) with a hazard ratio (HR) of 0·68 (95% CI 0·58–0·81; p<0·001). Progression-free survival was also longer in the TAS-102 group than in the placebo group (2·0 months vs 1·7 months [0·48, 0·41–0·57; p<0·001]); and a response was achieved in 1·6% of patients in the TAS-102 group versus 0·4% in the placebo group (p=0·29). The duration of response with TAS-102 ranged from 0·1–78 weeks. The most common adverse event in the TAS-102 group was grade 3 or 4 neutropenia occurring, in 35·9% of patients.

中文翻译：

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TAS-102加贝伐单抗：转移性结直肠癌的新标准？

对于无法手术切除的转移性结直肠癌患者，将提供连续护理以改善其总体结局。除以奥沙利铂和伊立替康为基础的疗法外，几乎没有其他治疗选择。RAS患者的数量甚至更少突变，占所有转移性结直肠癌患者的30-60％。当口服药物TAS-102在2017年获得美国食品和药物管理局的批准时，它为患有无法手术切除的转移性结直肠癌患者提供了另一种潜在选择。TAS-102通常被错误地吹捧为修饰的口服氟尿嘧啶，它由两个成分组成：三氟吡啶（一种核苷类似物）和盐酸替吡西酯（一种胸苷磷酸化酶抑制剂），以1·0：0·5的比例结合。Tipiracil可防止三氟吡啶快速降解，从而提高生物利用度。RECOURSE 3期试验将转移性结直肠癌（n = 800）的患者（2：1）随机分配接受TAS-102（35 mg / m ^2），第1-5天和第8-12天）或安慰剂。达到了总生存的主要终点，TAS-102组的中位总生存时间更长（安慰剂组为7·1个月，安慰剂组为5·3个月），危险比（HR）为0·68（95％CI） 0·58-0·81； p <0·001）。TAS-102组的无进展生存期也比安慰剂组长（2·0个月vs 1·7个月[0·48、0·41-0·57； p <0·001]）；在TAS-102组中，只有1·6％的患者获得了缓解，而在安慰剂组中，只有0·4％的患者获得了缓解（p = 0·29）。TAS-102的反应持续时间为0·1-78周。在TAS-102组中，最常见的不良事件是3或4级中性粒细胞减少，发生在35·9％的患者中。