Trifluridine–Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer
Mené sur 246 patients atteints d'un cancer colorectal de stade métastatique et réfractaire, cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout du bévacizumb à un traitement à base de trifluridine et tipiracil
Background: In a previous phase 3 trial, treatment with trifluridine–tipiracil (FTD–TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD–TPI in addition to bevacizumab has the potential to extend survival.
Methods: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD–TPI plus bevacizumab (combination group) or FTD–TPI alone (FTD–TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability).
Results: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD–TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD–TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD–TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67).
Conclusions: Among patients with refractory metastatic colorectal cancer, treatment with FTD–TPI plus bevacizumab resulted in longer overall survival than FTD–TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187. opens in new tab; EudraCT number, 2020-001976-14. opens in new tab.)
New England Journal of Medicine , résumé, 2022