BACKGROUND Trifluridine/tipiracil (FTD/TPI) plus bevacizumab has shown clinical benefit for metastatic colorectal cancer (mCRC) refractory to standard therapy. However, few data have been available for patients with pretreated mCRC who are intolerant of intensive therapy (vulnerable). METHODS We performed a multicenter retrospective study (WJOG14520G; TWILIGHT) of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC. Eligibility criteria included previous chemotherapy (although patients treated with all key cytotoxic agents, a fluoropyrimidine, oxaliplatin, and irinotecan, were excluded) and intolerance of full-dose combination therapy with oxaliplatin or irinotecan at the start of FTD/TPI plus bevacizumab. RESULTS The median age of 93 evaluable patients was 79 years (range, 21-90). Intolerance of intensive therapy was attributable to an older age in 60 (65%) patients, serious concomitant disease in 24 (26%) patients, and a poor performance status in 19 (20%) patients. FTD/TPI plus bevacizumab was administered as second-line treatment in 74 (80%) patients and as third- or fourth-line treatment in 19 (20%) patients. The objective response rate was 4.9% (95% confidence interval [CI], 1.4%-12.2%), and the disease control rate was 67.9% (95% CI, 56.6%-77.8%). With a median follow-up time of 21.6 months, median overall survival and progression-free survival were 18.6 months (95% CI, 12.1-23.2) and 6.3 months (95% CI, 5.0-8.3), respectively. Neutropenia of grade ≥3 developed in 50 (54%) patients, whereas 2 (2%) patients experienced febrile neutropenia, and no treatment-related death was observed. CONCLUSION Our data show the potential efficacy and acceptable safety profile of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC.

中文翻译：

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曲氟尿苷/替吡西加贝伐珠单抗治疗易受治疗的转移性结直肠癌患者：一项回顾性研究 (WJOG14520G)。

背景曲氟尿苷/替吡嘧啶 (FTD/TPI) 联合贝伐珠单抗已显示出对标准治疗难治的转移性结直肠癌 (mCRC) 的临床益处。然而，对于既往接受过治疗但不耐受强化治疗（脆弱）的转移性结直肠癌患者的数据很少。方法 我们针对接受过治疗的转移性结直肠癌 (mCRC) 弱势患者进行了一项 FTD/TPI 加贝伐单抗的多中心回顾性研究 (WJOG14520G; TWILIGHT)。资格标准包括既往化疗（尽管排除了接受所有关键细胞毒性药物、氟嘧啶、奥沙利铂和伊立替康治疗的患者）以及在 FTD/TPI 加贝伐单抗开始时对奥沙利铂或伊立替康全剂量联合治疗不耐受。结果 93 名可评估患者的中位年龄为 79 岁（范围为 21-90 岁）。60 名（65%）名患者对强化治疗不耐受，原因是年龄较大，24 名（26%）名患者存在严重伴随疾病，19 名（20%）名患者体能状态不佳。FTD/TPI 加贝伐单抗作为 74 名 (80%) 名患者的二线治疗，以及 19 名 (20%) 名患者的三线或四线治疗。客观缓解率为4.9%（95%置信区间[CI]，1.4%-12.2%），疾病控制率为67.9%（95% CI，56.6%-77.8%）。中位随访时间为 21.6 个月，中位总生存期和无进展生存期分别为 18.6 个月（95% CI，12.1-23.2）和 6.3 个月（95% CI，5.0-8.3）。50 名（54%）名患者出现≥3 级中性粒细胞减少症，而 2 名（2%）名患者出现发热性中性粒细胞减少症，未观察到与治疗相关的死亡。结论 我们的数据显示了 FTD/TPI 加贝伐珠单抗对于接受过治疗的易受转移性结直肠癌患者的潜在疗效和可接受的安全性。