On August 2, 2023, the FDA approved a new indication for trifluridine and tipiracil (Lonsurf; Taiho Oncology), in combination with bevacizumab, for metastatic colorectal cancer (CRC) previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti–vascular endothelial growth factor biologic therapy; and if RAS wild-type, an anti–epidermal growth factor receptor therapy.
The FDA granted this indication priority review status.
Trifluridine plus tipiracil was previously approved for this indication without bevacizumab in September 2015. Trifluridine plus tipiracil is also approved for the treatment of metastatic gastric or gastroesophageal junction adenocarcinoma after previous treatment with ≥2 lines of chemotherapy.
This new approval was based on the results of the phase 3 SUNLIGHT clinical trial (NCT04737187), a randomized, open-label, multicenter, global study of trifluridine plus tipiracil and bevacizumab compared with trifluridine plus tipiracil alone in 492 patients with metastatic CRC. These patients had received ≤2 previous chemotherapy regimens and had progressive disease or intolerance to the last regimen.
Overall survival (OS) and progression-free survival (PFS) were the study’s primary efficacy measures, and a significant improvement in OS was demonstrated in the patients who received trifluridine plus tipiracil and bevacizumab versus those who received trifluridine plus tipiracil alone (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.49-0.77; 1-sided P<.001).
In addition, the median OS was longer for patients receiving trifluridine plus tipiracil and bevacizumab (10.8 months; 95% CI, 9.4-11.8) than for those receiving trifluridine plus tipiracil alone (7.5 months; 95% CI, 6.3-8.6). Likewise, the median PFS was longer with trifluridine plus tipiracil and bevacizumab (5.6 months; 95% CI, 4.5-5.9) than with trifluridine plus tipiracil alone (2.4 months; 95% CI, 2.1-3.2; HR, 0.44; 95% CI, 0.36-0.54; 1-sided P<.001).
The most common (≥20%) adverse events or laboratory abnormalities with trifluridine plus tipiracil and bevacizumab are neutropenia, anemia, thrombocytopenia, fatigue, nausea, increased aspartate aminotransferase, increased alanine aminotransferase, increased alkaline phosphatase, decreased sodium, diarrhea, abdominal pain, and decreased appetite.
“The FDA approval of this combination provides patients with metastatic CRC an important new treatment option, one that has been shown to extend life in addition to other benefits and which I believe will change the treatment landscape for this patient population,” said Marwan Fakih, MD, Professor, Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, and lead US investigator for the SUNLIGHT trial. “Notably, the use of Lonsurf plus bevacizumab in these patients did not result in an increase in potentially intolerable side effects that might limit the utility of this combination.”
The recommended dose of trifluridine plus tipiracil is 35 mg/m2 orally with food, twice daily, on days 1 through 5 and on days 8 through 12 of each 28-day cycle. The complete dosing information for bevacizumab is available in the prescribing information.