New Combination Therapy for Treatment-refractory Colorectal Cancer 

The FDA approved a combination of trifluridine, tipiracil, and bevacizumab for the treatment of heavily pretreated metastatic colorectal cancer. 

The U.S. Food and Drug Administration (FDA) has approved trifluridine and tipiracil (Lonsurf), in combination with bevacizumab (Avastin), for the treatment of metastatic colorectal cancer following several prior rounds of therapy.  

Patients must have been previously treated with a chemotherapy regimen containing fluoropyrimidine, oxaliplatin, and irinotecan; a drug targeting the vascular endothelial growth factor (VEGF); and an inhibitor of the epidermal growth factor receptor (EGFR) if their tumor does not harbor mutations in the RAS gene. The combination of trifluridine and tipiracil was approved for the same indication, without the addition of bevacizumab, in 2015. 

Trifluridine and tipiracil are chemotherapy agents that combine to kill tumor cells. Trifluridine prevents DNA replication, causing cells to stall in the process of division and die. Tipiracil prevents the degradation of trifluridine and may additionally help prevent cell migration and the growth of new blood vessels around the tumor. Bevacizumab is a VEGF inhibitor that also prevents the growth of new blood vessels. 

This approval was based on results from SUNLIGHT, a randomized, open-label, multicenter, global, phase III clinical trial in which 492 patients with pretreated metastatic colorectal cancer were randomly assigned to receive trifluridine and tipiracil or trifluridine, tipiracil, and bevacizumab.  

Patients in the treatment arm that included bevacizumab had a 39% lower risk of death during the study than patients who did not receive bevacizumab. 

In the bevacizumab arm versus the control arm, patients had an overall survival of 10.8 months and 7.5 months, respectively, and a progression-free survival of 5.6 months and 2.4 months, respectively. 

Colorectal cancer is a type of cancer that forms in the large intestine. According to federal statistics, it was estimated that 153,020 individuals would be diagnosed with colorectal cancer and 52,550 patients would die of the disease in the U.S. in 2023. 

The FDA rendered its decision on August 2, 2023.