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

Joline S J Lim; Samuel G W Ow; Andrea L A Wong; Matilda X W Lee; Gloria H J Chan; Jia Li Low; Raghav Sundar; Joan R E Choo; Wan Qin Chong; Yvonne L E Ang; Bee Choo Tai; Soo Chin Lee

doi:10.1016/j.ejca.2023.113311

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

Eur J Cancer. 2023 Nov:193:113311. doi: 10.1016/j.ejca.2023.113311. Epub 2023 Aug 25.

Authors

Affiliations

¹ Department of Hematology-Oncology, National University Cancer Institute, Singapore, Singapore; Experimental Therapeutics Programme, Cancer Science Institute, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore.
² Department of Hematology-Oncology, National University Cancer Institute, Singapore, Singapore.
³ Department of Hematology-Oncology, National University Cancer Institute, Singapore, Singapore; Experimental Therapeutics Programme, Cancer Science Institute, Singapore, Singapore.
⁴ Department of Hematology-Oncology, National University Cancer Institute, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore.
⁵ Saw Swee Hock School of Public Health, National University Singapore, Singapore.
⁶ Department of Hematology-Oncology, National University Cancer Institute, Singapore, Singapore; Experimental Therapeutics Programme, Cancer Science Institute, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore. Electronic address: csilsc@nus.edu.sg.

PMID: 37717281
DOI: 10.1016/j.ejca.2023.113311

Abstract

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, 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 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.

Keywords: Chemotherapy; FTD/TPI; Metastatic breast cancer.