Colon to Rectum

N Engl J Med. 2023;388(18):1657–67

Prager GW, Taieb J, Fakih M, Ciardiello F, Van Cutsem E, Elez E, Cruz FM, Wyrwicz L, Stroyakovskiy D, Pápai Z, Poureau PG, Liposits G, Cremolini C, Bondarenko I, Modest DP, Benhadji KA, Amellal N, Leger C, Vidot L, Tabernero J; SUNLIGHT Investigators

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.

Dr. J. Tabernero, Department of Medical Oncology, Vall d’Hebron Hospital Campus, Barcelona, Spain,
E-Mail: jtabernero@vhio.net

DOI: 10.1056/nejmoa2214963

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