Real-World Comparison of Trifluridine–Tipiracil with or Without Bevacizumab in Patients with Refractory Metastatic Colorectal Cancer

Background/Objectives: Patients with metastatic colorectal cancer (mCRC) who are refractory to standard chemotherapy face limited treatment options. While trifluridine–tipiracil (FTD–TPI) and regorafenib have shown modest efficacy in prior clinical trials, recent data from the SUNLIGHT trial demonstrated that combining FTD–TPI with bevacizumab (FTD–TPI+BEV) may improve overall survival compared to FTD–TPI alone. However, supporting evidence from real-world populations remains scarce. Methods: This retrospective study assessed the real-world effectiveness and safety of FTD–TPI+BEV versus FTD–TPI monotherapy in patients with refractory mCRC treated at two institutions from June 2020 to October 2024. Results: A total of 106 patients were included, with 47 treated with FTD–TPI+BEV and 59 with FTD–TPI alone. Median progression-free survival (PFS) was significantly longer with FTD–TPI+BEV compared to FTD–TPI alone (4.1 vs. 2.1 months; HR = 0.56; p = 0.004), while median overall survival showed a non-significant trend favoring FTD–TPI+BEV (8.4 vs. 6.3 months; HR = 0.74; p = 0.189). The disease control rate was also significantly higher with FTD–TPI+BEV (59.6% vs. 25.4%, p = 0.001). Subgroup analyses showed consistent PFS benefits. Grade 3–5 adverse events occurred at comparable rates between groups. Conclusions: FTD–TPI+BEV may represent a preferred salvage treatment option for refractory mCRC.