Colon to Rectum
N Engl J Med. 2023;388(18):1657–67
Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer
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 bevaci-zumab has the potential to extend survival.
Methods: The authors randomly assigned, in a 1:1 ratio, adult patients who had received no more than 2 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 indi-cating 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 [HR] for death = 0.61; 95% confidence interval [CI]: 0.49–0.77; p < 0.001). The median progres-sion-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (HR for disease progression or death = 0.44; 95% CI: 0.36–0.54; 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 (HR = 0.54; 95% CI: 0.43–0.67).
Conclusions: Among patients with refractory metastatic colorectal cancer, treatment with trifluridine-tipiracil (FTD-TPI) plus bevacizumab resulted in longer overall survival than FTD-TPI alone.