氟嘧啶类药物常用于治疗转移性乳腺癌（MBC），三氟胞嘧啶/替匹利（FTD/TPI）在之前接受氟嘧啶类药物治疗的结直肠癌和胃癌患者中显示出活性。我们在单臂II期研究中研究了FTD/TPI在具有或不具有之前氟嘧啶类药物暴露情况的MBC患者中的作用。MBC患者首先入组进行剂量确认阶段，随后分为两个平行队列，分别为具有（队列A）和不具有（队列B）之前氟嘧啶类药物暴露的患者，然后接受FTD/TPI治疗。每个队列的主要目标包括确定无进展生存期（PFS），次要目标包括确定客观缓解率（ORR）、安全性和耐受性。共有74名患者（队列A 42名，队列B 32名）入组，所有患者均可评估毒性和生存情况，其中72名可评估治疗反应。队列A和B的中位PFS分别为5.7个月（95%置信区间 3.8-8.3）和9.4个月（95% CI 5.5-14.0）。无论是否有过氟嘧啶类药物暴露，都观察到了治疗反应，队列A和B的ORR分别为19.5%（95% CI 8.8-34.9）和16.1%（95% CI 5.5-33.7），6个月的临床益处率分别为56.1%（95% CI 39.7-71.5）和61.3%（95% CI 42.2-78.2）。安全性与FTD/TPI已知的毒性相符，包括白细胞减少、疲劳、恶心和食欲不振，可以通过调整剂量减轻这些毒性。FTD/TPI显示出有希望的抗肿瘤活性，毒性可控，在MBC患者中是一个临床有效的选择。版权所有 © 2023 Elsevier Ltd. 保留所有权利。

Fluoropyrimidines are commonly used in the treatment of metastatic breast cancer (MBC), and trifluridine/tipiracil (FTD/TPI) has shown activity in patients with colorectal and gastric cancers despite prior exposure to fluoropyrimidines. We investigate the role of FTD/TPI in patients with MBC with or without prior fluoropyridines in a single-arm phase II study.Patients with MBC were enroled first into a run-in dose confirmation phase, followed by two parallel cohorts including patients with (Cohort A) and without (Cohort B) prior exposure to fluoropyrimidines, where they were treated with FTD/TPI. Primary objectives for each cohort included determination of progression-free survival (PFS), and secondary objectives included determination of objective response rates (ORR), safety, and tolerability.Seventy-four patients (42 Cohort A, 32 Cohort B) were enroled, all of whom were evaluable for toxicity and survival, with 72 evaluable for response. Median PFS was 5.7 months (95% confidence interval 3.8-8.3) and 9.4 months (95% CI 5.5-14.0) respectively in Cohorts A and B. Responses were observed regardless of prior exposure to fluoropyrimidines, with ORR of 19.5% (95% CI 8.8-34.9) and 16.1% (95% CI 5.5-33.7) in Cohorts A and B, and 6-month clinical benefit rates of 56.1% (95% CI 39.7-71.5) and 61.3% (95% CI 42.2-78.2) respectively. The safety profile was consistent with known toxicities of FTD/TPI, including neutropenia, fatigue, nausea, and anorexia, mitigated with dose modifications.FTD/TPI showed promising antitumour activity with manageable toxicity and is a clinically valid option in patients with MBC.Copyright © 2023 Elsevier Ltd. All rights reserved.