Trifluridine and Tipiracil Plus Bevacizumab Approved for Previously Treated Metastatic Colorectal Cancer

The FDA has approved trifluridine and tipiracil (Lonsurf®, Taiho Oncology, Inc.) in combination with bevacizumab (Avastin®, Genentech, Inc.) for treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti–vascular endothelial growth factor (VEGF) biological therapy, and—if rat sarcoma (RAS) wild-type—an anti–epidermal growth factor receptor (EGFR) therapy. The FDA formerly approved single-agent trifluridine and tipiracil for previously treated colorectal cancer in September 2015.  

Why it matters: “In a previous phase 3 trial, treatment with trifluridine-tipiracil prolonged overall survival among patients with metastatic colorectal cancer,” wrote Gerald Prager, MD, PhD, Director of the Gastrointestinal Cancer Program at the Medical University and Comprehensive Cancer Center of Vienna, Austria, and colleagues, in their published results of the SUNLIGHT trial (NCT04737187), on which approval was based. “Preliminary data from single-group and randomized phase 2 trials suggest that treatment with trifluridine and tipiracil in addition to bevacizumab has the potential to extend survival.”

What they studied: The safety and efficacy of trifluridine and tipiracil with bevacizumab were studied in the phase 3, international, open-label, two-arm trial in which 492 patients with mCRC who received two prior chemotherapy regimens and demonstrated disease progression or intolerance to the last regimen were randomized 1:1. Patients randomized to the experimental arm received 35 mg/m2 trifluridine and tipiracil, administered two times a day by mouth on Days 1 to 5 and 8 to 12 of each 28-day cycle, in combination with 5 mg/kg bevacizumab, administered intravenously on Day 1 and Day 15 of each cycle. Patients randomized to the control arm received trifluridine and tipiracil alone, administered identically to the experimental arm.

The primary end points measured were overall survival and progression-free survival, with a secondary end point of safety.

What they found: Trifluridine and tipiracil plus bevacizumab demonstrated a statistically significant improvement in overall survival at a median of 10.8 months compared with a median of 7.5 months for those receiving trifluridine and tipiracil alone. Progression-free survival in the experimental arm was seen at a median of 5.6 months compared with 2.4 months in the control arm.

Adverse events: The most common adverse events or laboratory abnormalities in ≥20% of those receiving trifluridine and tipiracil plus bevacizumab are neutropenia, anemia, thrombocytopenia, fatigue, nausea, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased alkaline phosphatase, decreased sodium, diarrhea, abdominal pain, and decreased appetite.

Conclusion: “Among patients with refractory metastatic colorectal cancer, treatment with trifluridine and tipiracil plus bevacizumab resulted in longer overall survival than trifluridine and tipiracil alone,” concluded Dr. Prager and colleagues in their results.

Instructions: The recommended dosage of trifluridine and tipiracil is 35 mg/m2 orally, twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. Please refer to the bevacizumab prescribing information for dosage instructions.

For More Information

Prager GW, Taieb J, Fakih M, et al (2023). Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer. N Engl J Med, 388(18):1657-1667. DOI:10.1056/NEJMoa2214963 (2023). Phase III study of trifluridine/tipiracil in combination with bevacizumab vs trifluridine/tipiracil single agent in patients with refractory metastatic colorectal cancer (SUNLIGHT). NLM identifier: NCT04737187.

Lonsurf® (trifluridine and tipiracil) prescribing information (2023). Taiho Oncology Inc. Available at:

Avastin® (bevacizumab) prescribing information (2023). Genentech Inc. Available at:

US Food and Drug Administration (2023). FDA approves trifluridine and tipiracil with bevacizumab for previously treated metastatic colorectal cancer. Available at:

Image credit: Calicut Medical College. Licensed under CC BY-SA 4.0

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