Clinical outcomes of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil or regorafenib in metastatic colorectal cancer: a multicenter cohort study.

BACKGROUND

In patients with pretreated metastatic colorectal cancer (mCRC), trifluridine/tipiracil (FTD-TPI) + bevacizumab has superior efficacy compared with FTD-TPI alone. However, real-world data on outcomes and comparisons with other established therapies including regorafenib are scarce. Additionally, evidence suggests that molecular alterations, such as KRASG12 mutations, may affect FTD-TPI efficacy. We aimed to compare clinical outcomes of patients with mCRC treated with FTD-TPI + bevacizumab, FTD-TPI, or regorafenib across molecular subgroups.

PATIENTS AND

METHODS

This retrospective cohort study included 509 patients treated at six Austrian cancer centers between January 2015 and December 2022. The primary outcome was progression-free survival (PFS), with overall survival (OS) and disease control rate (DCR) as secondary outcomes. Between-group differences were analyzed using Cox and logistic regression. A propensity score analysis using inverse probability of treatment weighting (IPTW) was conducted. Flexible parametric models and restricted mean survival time (RMST) analyses were used to account for time-dependent differences in PFS/OS.

RESULTS

In propensity score analysis, patients treated with FTD-TPI + bevacizumab (n = 130) versus FTD-TPI (n = 227) alone or regorafenib (n = 152) had longer PFS [IPTW-adjusted hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.51-0.92, P = 0.012] and higher DCR (IPTW-adjusted odds ratio 3.35, 95% CI 1.81-6.20, P < 0.001). The IPTW-adjusted HR for OS was 0.80 (95% CI 0.58-1.12, P = 0.203). A modest OS benefit of FTD-TPI + bevacizumab was observed within the first 12 months. In RMST-analysis, OS was 12.1 months (95% CI 11.4-12.8 months) for FTD-TPI + bevacizumab compared with 10.6 months (95% CI 9.9-11.2 months) for the controls (P = 0.003). Outcomes were consistent across key molecular subsets, including KRAS and KRASG12 mutations.

CONCLUSIONS

In this large real-world cohort of patients with mCRC, FTD-TPI + bevacizumab was associated with improved PFS and DCR compared with FTD-TPI or regorafenib, with consistent benefit across most molecular subgroups, including KRASG12 mutations.