FDA Approves Trifluridine/Tipiracil Plus Bevacizumab in mCRC

• The basis of this approval comes from positive findings from the phase 3 SUNLIGHT trial (NCT04737187) of trifluridine/tipiracil (Lonsurf) plus bevacizumab (Avastin) vs trifluridine/tipiracil alone in patients with refractory metastatic colorectal cancer (mCRC).

• The FDA previously approved single-agent trifluridine/tipiracil for this indication in September 2015.

• The recommended dose of trifluridine/tipiracil is 35 mg/m² orally twice daily with food on days 1-5 and days 8 -12 of each 28-day cycle.

The FDA has approved trifluridine/tipiracil alone or in combination with bevacizumab for the treatment of adult patients with refractory mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, an anti-EGFR therapy, or if they are RAS wild-type.¹ 

Results from the pivotal phase 3 SUNLIGHT trial support the approval as the investigational combination of trifluridine/tipiracil with bevacizumab led to statistically significant and clinically meaningful improvements in overall survival and progression-free survival (PFS) among patients with refractory mCRC after disease progression or intolerance on 2 prior chemotherapy regimens vs trifluridine/tipiracil alone.² 

With a total of 246 patients assigned to each group, the median overall survival was 10.8 months among those given the combination vs 7.5 months for those given trifluridine/tipiracil alone (HR, 0.61; 95% CI, 0.49-0.77; P <.001). The median PFS was 5.6 months with the combination group vs 2.4 months in the trifluridine/tipiracil group (HR, 0.44; 95% CI, 0.36-0.54; P <.001).

The median time to worsening of ECOG performance status was significantly delayed among those given trifluridine/tipiracil and bevacizumab at 9.3 months vs 6.3 months with trifluridine/tipiracil alone (HR, 0.54; 95% CI, 0.43-0.67). Additionally, the safety profile of the combination was consistent with that of each agent alone. The most common AEs reported in both groups included neutropenia, nausea, and anemia, and there were no treatment-related deaths reported.

REFERENCES:

1. FDA approves trifluridine and tipiracil with bevacizumab for previously treated metastatic colorectal cancer. News release. FDA. August 2, 2023. Accessed August 2, 2023. https://tinyurl.com/ys3ej7m4

2. Prager GW, Taieb J, Fakih M, et al. Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer. N Engl J Med. 2023;388(18):1657-1667. doi:10.1056/NEJMoa2214963