The Danish randomized trial of trifluridine–tipiracil and bevacizumab in metastatic colorectal cancer: final survival and post hoc neutropenia and quality-of-life analyses

Background In 2020, we published the first randomized trial demonstrating the efficacy of trifluridine–tipiracil (FTD–TPI) with bevacizumab compared with FTD–TPI monotherapy in chemorefractory metastatic colorectal cancer. This study aims to: (i) analyze final survival data, (ii) perform post hoc analyses of the prognostic role of chemotherapy-induced neutropenia (CIN), and (iii) assess time to deterioration of performance status (PS) as a measure associated with quality of life in post hoc analyses. Materials and methods The Kaplan–Meier method and Cox proportional hazards models were used to analyze final survival data for all 93 patients included in the trial. CIN was modeled as a time-varying covariate. Results Progression-free survival was 4.6 months [95% confidence interval (CI) 3.7-6.5] with FTD–TPI plus bevacizumab versus 2.4 months (95% CI 1.8-3.6) with FTD–TPI; hazard ratio (HR) 0.47 (95% CI 0.31-0.73). Overall survival was 10.0 months (95% CI 8.1-12.7) with FTD–TPI plus bevacizumab versus 6.0 months (95% CI 5.5-7.9) with FTD–TPI; HR 0.55 (95% CI 0.36-0.84). CIN was associated with reduced hazard of progression; HR 0.32 (95% CI 0.15-0.70) for FTD–TPI and HR 0.22 (95% CI 0.10-0.52) for FTD–TPI plus bevacizumab. CIN was also associated with reduced hazard of death: HR 0.62 (95% CI 0.39-0.97) for FTD–TPI and HR 0.64 (95% CI 0.35-1.17) for FTD–TPI plus bevacizumab. Patients receiving FTD–TPI plus bevacizumab had longer time to PS worsening to ≥2: HR 0.39 (95% CI 0.25-0.61). Conclusions Our findings support the superiority of FTD–TPI plus bevacizumab over FTD–TPI in prolonging survival and maintaining PS. CIN was associated with improved survival outcomes.