Phase II study of Trifluridine/Tipiracil (FTD/TPI) in metastatic breast cancers with or without prior exposure to fluoropyrimidines
Mené sur 74 patientes atteintes d'un cancer du sein de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement combinant trifluridine et tipiracile
Background: Fluoropyrimidines are commonly used in 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 enrolled 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. Results: Seventy-four patients (42 Cohort A, 32 Cohort B) were enrolled, all of whom were evaluable for toxicity and survival, with 72 evaluable for response. Median PFS was 5.7 months (95% CI 3.8 to 8.3) and 9.4 months (95% CI 5.5 to 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 to 34.9) and 16.1% (95% CI 5.5 to 33.7) in Cohorts A and B, and 6-month clinical benefit rates of 56.1% (95% CI 39.7 to 71.5) and 61.3% (95% CI 42.2 to 78.2) respectively. 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 antitumor activity with manageable toxicity, and is a clinically valid option in patients with MBC.