A real-world study of Trifluridine/Tipiracil (TAS-102) combined with bevacizumab as the late-line treatment of metastatic colorectal cancer

Trifluridine/Tipiracil (TAS-102) is an effective agent for the late-line treatment of metastatic colorectal cancer (mCRC). Combining TAS-102 with bevacizumab improves outcomes but may increase adverse events. We conducted a real-world, retrospective, exploratory comparison of two dosing schedules (bi-weekly vs. four-weekly) to describe efficacy, safety, and potential molecular and clinical correlates. We analyzed patients with mCRC who were treated with TAS-102 in combination with bevacizumab as late-line therapy from January 2020 to February 2023. Regimen assignment followed physician-patient shared decision-making based on clinical factors and local practice changes after emerging evidence, not randomization. Endpoints included progression-free survival (PFS), overall survival (OS), adverse events (AEs). Analyses were exploratory and hypothesis-generating, with multivariable Cox models for selected covariates. A total of 92 patients were enrolled in this study. Median PFS was 3.2 months (bi-weekly) vs. 3.7 months (four-weekly), and median OS was 10.0 vs. 9.3 months, with no statistically significant differences. KRAS mutation was associated with inferior OS (7.7 vs. 11.8 months; P = 0.018), whereas TP53 was not. Eastern Cooperative Oncology Group performance status (ECOG-PS) = 2 independently predicted shorter PFS and OS; prior bevacizumab exposure correlated with shorter PFS but not OS. Common adverse events in patients were neutropenia (63.0%), leukopenia (67.0%), anemia (44.6%), malaise (55.4%), nausea (45.7%), anorexia (31.5%), and diarrhea (23.9%). In this retrospective, real-world study, the two regimens demonstrated comparable disease control, and the bi-weekly regimen appeared to be better tolerated, representing a reasonable potential alternative. Nevertheless, these findings should be interpreted as exploratory, and future prospective studies are warranted.