Clinical outcomes of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil or regorafenib in metastatic colorectal cancer: a multicenter cohort study
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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 KRAS G12 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 KRAS G12 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 KRAS G12 mutations.
Source: ESMO Open
Institutions: Medical University of Graz, Paracelsus Medical University, Universitätsklinikum St. Pölten, Karl Landsteiner University of Health Sciences, Landeskrankenhaus Feldkirch, Innsbruck Medical University, Universität Innsbruck, BioTechMed-Graz, Austrian Breast & Colorectal Cancer Study Group, Harvard University, Massachusetts General Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,910
OpenAlex ID: W7140572365