Long-term responders to trifluridine/tipiracil plus bevacizumab in previously treated metastatic colorectal cancer: Results from the BeTAS real-world study.

Abstract

3583 Background: The phase III SUNLIGHT trial established trifluridine/tipiracil plus bevacizumab (FTD/TPI+BEV) as a standard treatment option for metastatic colorectal cancer (mCRC) after failure of at least two prior regimens. However, limited evidence exists regarding patients achieving durable benefit in routine clinical practice. We aimed to characterize the prevalence, clinical features, and outcomes of long-term responders treated with FTD/TPI plus bevacizumab in a large real-world cohort. Methods: BeTAS is a multicenter ambispective real-world study conducted within the Galician Research Group on Gastrointestinal Tumors. Consecutive patients with previously treated mCRC receiving FTD/TPI+BEV after failure or intolerance to ≥2 prior regimens were included. Long-term responders (LTRs) were defined using a pre-specified landmark of progression-free survival (PFS) ≥9 months. Baseline characteristics, treatment response, and survival outcomes were compared between LTRs and non-LTRs. Overall survival (OS) was assessed using a 9-month landmark analysis to minimize immortal time bias. Survival was estimated using the Kaplan–Meier method and compared using the log-rank test. Multivariable Cox regression was performed. Results: Among 576 patients, median PFS and OS were 4.9 months (95% CI 4.3–5.5) and 10.8 months (95% CI 9.8–11.9), respectively. LTRs accounted for 20.3% of the cohort (n=117). Compared with non-LTRs, LTRs more frequently had ≤2 metastatic sites (83.8% vs 67.5%, p =0.001), absence of liver metastases (28.4% vs 16.7%, p =0.004), longer time from metastatic diagnosis ( p =0.046), and Tabernero best prognostic characteristics ( p =0.007). Among evaluable patients, objective response rate was higher in LTRs (22.1% vs 5.5%, p <0.001), as was disease control rate (100% vs 39.0%, p <0.001). Median PFS was 15.3 versus 3.6 months, and landmark OS was 23.5 versus 8.1 months (both p <0.001). Long-term response remained independently associated with improved OS (HR 0.19, 95% CI 0.14–0.26; p <0.001). Conclusions: In real-world practice, approximately one in five previously treated patients with mCRC achieve durable benefit with FTD/TPI+BEV. Identification of clinical factors associated with long-term response may support improved patient selection in later-line treatment.