Trifluridine–Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer

• Published in: The New England journal of medicine Vol. 388; no. 18; pp. 1657 - 1667
• Main Authors: Prager, Gerald W., Taieb, Julien, Fakih, Marwan, Ciardiello, Fortunato, Van Cutsem, Eric, Elez, Elena, Cruz, Felipe M., Wyrwicz, Lucjan, Stroyakovskiy, Daniil, Pápai, Zsuzsanna, Poureau, Pierre-Guillaume, Liposits, Gabor, Cremolini, Chiara, Bondarenko, Igor, Modest, Dominik P., Benhadji, Karim A., Amellal, Nadia, Leger, Catherine, Vidot, Loïck, Tabernero, Josep
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 04.05.2023
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antiviral drugs; Bevacizumab; Bevacizumab - adverse effects; Bevacizumab - therapeutic use; Cancer; Cancer therapies; Chemotherapy; Clinical trials; Colonic Neoplasms - drug therapy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Confidence intervals; Design; Disease control; Drug Combinations; Frontotemporal dementia; Gastroenterology; Gastrointestinal Tract Cancer; Hematology; Humans; Laboratories; Metastases; Metastasis; Monoclonal antibodies; Neutropenia; Oncology; Pyrrolidines - adverse effects; Pyrrolidines - therapeutic use; Questionnaires; Rectal Neoplasms - drug therapy; Survival; Targeted cancer therapy; Treatments in Oncology; Trifluridine - adverse effects; Trifluridine - therapeutic use; Tumors; Uracil; Vascular endothelial growth factor
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa2214963

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. 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). 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). 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; EudraCT number, 2020-001976-14.).