Phase II study of trifluridine/tipiracil in metastatic breast cancers with or without prior exposure to fluoropyrimidines

Background: 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.Methods: Patients with MBC were enroled first into a run-in dose confirmation phase, fol-lowed 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 ob-jectives for each cohort included determination of progression-free survival (PFS), and sec-ondary objectives included determination of objective response rates (ORR), safety, and tolerability.Results: 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. Conclusion: FTD/TPI showed promising antitumour activity with manageable toxicity and is a clinically valid option in patients with MBC.(c) 2023 Elsevier Ltd. All rights reserved.