377P - Phase II study of trifluridine/tipiracil in pre-treated patients with ER-positive, HER2-negative metastatic breast cancer: A Dutch BOOG (2019-01 TIBET) study

Background

Few treatment options are available for patients with metastatic breast cancer (MBC) after standard early lines of chemotherapy. Trifluridine/tipiracil (FTD/TPI, alias TAS-102) has demonstrated survival benefit in heavily pre-treated patients with metastatic colorectal and gastric cancer, refractory to fluoropyrimidines. Advantages of FTD/TPI are oral use, no hand/foot syndrome, lack of cardiotoxicity and no dependency on the DPD enzyme. This phase II study investigated the efficacy of FTD/TPI in patients with ER+, HER2- MBC pre-treated with regular endocrine therapy lines and at least 2 lines of chemotherapy, including a taxane and capecitabine.

Methods

This trial was an open-label, single-arm, multicenter phase II study conducted in ten Dutch hospitals. The primary endpoint was progression-free survival (PFS) rate at 8 weeks. Secondary endpoints included PFS, overall survival (OS), best overall response, safety and quality of life. The primary endpoint was considered met, justifying further research into this treatment regimen, if the lower boundary of the 80% confidence interval (CI) exceeded 30%.

Results

Fifty eligible patients were enrolled, with a median of 3 previous endocrine therapy lines and 2 chemotherapy lines for MBC. The PFS rate at 8 weeks was 64.0% (95% CI: 50.1-75.9%; 80% CI: 55.0-72.1%), thereby meeting the primary endpoint of this study. The median PFS was 5.4 months (95% CI: 2.0-7.2 m), with the duration of previous capecitabine treatment showing no effect on PFS (p = 0.616). The PFS rate at 1-year was 23.7% (95% CI: 12.1-37.4%). One patient had a complete overall response. The median OS was 14.0 months (95% CI: 8.8-17.8 m). The safety profile of FTD/TPI aligned with expected toxicities, including leucopenia, neutropenia, and fatigue. There were no relevant changes in quality of life scores during treatment.

Conclusions

FTD/TPI demonstrated highly promising efficacy in heavily pre-treated patients with MBC, despite prior exposure to a fluoropyrimidine. The advantages of oral administration and the maintenance of quality of life suggest that it holds potential as a viable treatment option. Preparations are underway to initiate a randomized phase III trial.

Clinical trial identification

NCT04489173 (release date: 28-07-2020).

Editorial acknowledgement

Legal entity responsible for the study

Borstkanker Onderzoek Groep Borstkanker Onderzoek Groep Borstkanker Onderzoek Groep (BOOG).

Funding

Servier.

Disclosure

R.H. Mathijssen: Financial Interests, Institutional, Invited Speaker: Bayer, Novartis; Financial Interests, Institutional, Advisory Board: Servier, NaDeNo Nanoscience; Financial Interests, Institutional, Research Grant, Investigator-initiated research: Astellas, Bayer, Cristal Therapeutics, Pfizer, Roche, Sanofi, Servier, Boehringer-Ingelheim, Novartis, Nordic Pharma; Financial Interests, Institutional, Coordinating PI: Pamgene; Financial Interests, Institutional, Funding: Echo Pharmaceuticals, Deuter Oncology. M. De Boer: Financial Interests, Personal, Other, Member of Data Safety Monitoring Board: Novartis; Financial Interests, Institutional, Invited Speaker: Gilead, Pfizer; Financial Interests, Institutional, Funding, Institutional research grant: Novartis; Financial Interests, Institutional, Research Grant, Institutional research grant: E. Lilly; Financial Interests, Institutional, Research Grant: Pfizer, Roche, AstraZeneca, Daiichi Sankyo, Gilead. M.M. van Rosmalen: Financial Interests, Personal, Writing Engagement, Poster at ONS and article about 'Models of Best Practice - Nurse integration into the BRCA testing pathway': Astrazeneca; Financial Interests, Personal, Other, Creating information material for trastuzumab-deructecan with other nurse practitioners: Astrazeneca. All other authors have declared no conflicts of interest.