Effectiveness of FTD/TPI plus bevacizumab and impact of prior bevacizumab exposure in patients with mCRC: the Italian FLOWER study.

Background: The SUNLIGHT trial established trifluridine/tipiracil (FTD/TPI) plus bevacizumab as a new later-line standard in metastatic colorectal cancer (mCRC). However, evidence in real-world populations-often older and more heterogeneous-remains limited. This study evaluated the effectiveness and safety of FTD/TPI plus bevacizumab in a large, unselected real-world mCRC population and aimed to identify potential predictive factors associated with response to this treatment. Patients and methods: We conducted a retrospective, multicenter analysis of patients with refractory mCRC treated with FTD/TPI plus bevacizumab across 15 Italian centers. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and safety. Results: 297 patients were included. Median age was 61.8 years, and 79.1% had ≥2 metastatic sites. Most patients (89.9%) had prior bevacizumab exposure, and 35.4% had received ≥3 treatment lines. ORR was 7.4%, and the disease control rate was 54.2%. Median PFS was 5.3 months [95% confidence interval (CI) 4.5-6.5 months], and median OS was 11.9 months (95% CI 10.5-14.3 months). Eastern Cooperative Oncology Group performance status, tumor sidedness, metastatic burden, and time from metastatic diagnosis to treatment initiation results were statistically associated with OS. Any grade adverse events occurred in 243 (81.8%) patients, and grade 3-4 events in 152 (52.2%); grade 3-4 neutropenia was the most frequent and emerged in 35.4% of patients, while non-hematologic toxicities were mostly low grade. Conclusions: In this unselected real-world population, FTD/TPI plus bevacizumab demonstrated clinically meaningful activity and a tolerable safety profile. Outcomes were consistent with the SUNLIGHT trial, supporting the routine use of this combination in later-line option in mCRC.