Real-world outcomes and prognostic factors of trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer: a multicenter study in Spain

Background Trifluridine/tipiracil plus bevacizumab (FTD/TPI+BEV) has demonstrated survival benefit in patients with metastatic colorectal cancer (mCRC) after failure of at least two prior treatment regimens in the phase III SUNLIGHT trial (NCT04737187), which compared FTD/TPI+BEV with FTD/TPI monotherapy; however, real-world evidence remains limited. The BeTAS real-world study evaluated the real-world effectiveness and safety of FTD/TPI+BEV in Spanish routine clinical practice. Patients and methods This ambispective, multicenter observational study included 549 patients with mCRC treated with FTD/TPI+BEV across 19 Spanish university hospitals [retrospectively (2019-2023) and prospectively (from 2024 onward)]. Outcomes included overall survival (OS), progression-free survival (PFS), and tumor response according to RECIST version 1.1. Safety was assessed using Common Terminology Criteria for Adverse Events version 5.0. Univariate and multivariate analyses evaluated baseline and treatment-emergent prognostic factors. Results Median OS was 10.8 months and median PFS was 5.0 months. The objective response rate was 9.6% and the disease control rate was 51.9%. Treatment efficacy was independent of sex, RAS/BRAF mutational status, and prior anti–vascular endothelial growth factor exposure. Improved survival outcomes were observed in patients with lower metastatic burden, longer time from metastatic diagnosis, Eastern Cooperative Oncology Group performance status 0-1, left-sided primary tumors, and favorable baseline prognostic classification. Development of grade 3-4 neutropenia and primary prophylactic granulocyte colony-stimulating factor (G-CSF) use were independently associated with prolonged OS and PFS; however, these findings should be interpreted cautiously given the observational design. Neutropenia was the most frequent grade ≥3 adverse event. Two treatment-related deaths were reported. Conclusions FTD/TPI+BEV is effective and well tolerated in Spanish real-world clinical practice, consistent with SUNLIGHT. Baseline prognostic classification, performance status, metastatic burden, and treatment-emergent factors were associated with clinical outcomes. The observed associations for grade 3-4 neutropenia and primary prophylactic G-CSF use should be considered exploratory and hypothesis-generating.