Real-world efficacy of trifluridine/tipiracil and bevacizumab combination according to baseline prognostic factors: The BeTAS study.

Abstract

3578 Background: The Sunlight Trial demonstrated that trifluridine-tipiracil (FTD/TPI) and bevacizumab (BEV) significantly improved Overall Survival (OS) and Progression-Free Survival (PFS) in patients with pretreated metastatic colorectal cancer (mCRC) after two treatment lines. However, the real-world efficacy and influence of baseline prognostic factors are not fully understood. Methods: This retrospective, observational, multicenter study across 18 Spanish hospitals included mCRC patients treated with FTD/TPI+BEV in a real-world setting. Prognostic factors were analyzed, including Tabernero's subgroups, which categorize patients according to time to diagnosis from first metastasis ( < 18 vs. > 18 months), number of metastatic sites ( < 3 vs. > 3), and liver metastasis (yes vs. no). Patients were grouped into Best (BPC), Good (GPC), and Poor (PPC) prognostic categories. Results: 398 patients were treated from July 2019 to December 2024. Median age was 67 years (range 26-92), 65.8% male, and 88.4% had ECOG PS 0-1. 56.3% had RAS mutations. Liver metastases were present in 75.3%, 27.7% had > 3 metastatic sites, and 28.2% had < 18 months from diagnosis of first metastasis, resulting in 47.2% of patients categorized as PPC. 67.8% received FTD/TPI+BEV as third-line treatment. ORR was 6.8%, and DCR was 49.9%. With a median follow-up of 14 months, median PFS was 4.9 months (95% CI, 4.1-5.1) and OS was 10.8 months (95% CI, 9.2-12.4). Neutropenia was the most common toxicity, with 33.1% of patients experiencing grade 3-4 neutropenia. OS by ECOG PS 0 vs. 1 vs. 2 was 12.5 vs. 11.1 vs. 5.7 months (p < 0.0001). PFS by ECOG PS 0 vs. 1 vs. 2 was 5.6 vs. 4.9 vs. 3.5 months (p = 0.102). OS by BPC vs. GPC vs. PPC was 18.3 vs. 12.8 vs. 7.5 months (p < 0.0001), and PFS was 7.3 vs. 5.8 vs. 3.7 months (p < 0.0001). OS in patients with grade 3-4 neutropenia vs. no neutropenia was 17.7 vs. 8.1 months (p < 0.0001), and PFS was 8.7 vs. 3.9 months (p < 0.0001). Conclusions: Our series confirms the effectiveness of FTD/TPI + BEV in real-world clinical practice, with a median OS of 10.8 months and a median PFS of 4.9 months. The ECOG performance status, Tabernero subgroups, and the occurrence of grade 3-4 neutropenia help identify patients who may obtain the maximum benefit from FTD/TPI + BEV treatment. Interestingly, all subgroups analyzed showed a greater benefit compared to the outcomes previously reported for FTD/TPI monotherapy, highlighting the potential of this combination in clinical practice.