FDA Approves Trifluridine and Tipiracil with Bevacizumab for Metastatic Colorectal Cancer (mCRC) with Specific Mutation

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On August 2, 2023, the U.S. Food and Drug Administration approved trifluridine and tipiracil (LONSURF) with bevacizumab for the treatment of metastatic colorectal cancer (mCRC) in patients who have previously received a maximum of two chemotherapy agents and showed progression or intolerance to the last agent. Single-agent LONSURF was approved for the same indication in September 2015.


Study ID number: NCT04737187


Approval was based on the SUNLIGHT trial (NCT04737187), a randomized, open-label, multicenter, global study that included 492 patients with mCRC. These patients had previously received regimens based on fluoropyrimidine, oxaliplatin, and irinotecan; anti-VEGF biological therapy; and if the tumor showed RAS wild-type mutation, an anti-EGFR therapy. Patients were confirmed to have mCRC with the necessary mutations using an FDA-approved test.


Trifluridine and tipiracil with bevacizumab were administered orally at 35 mg/m2 twice daily with food on days 1 through 5 and days 8 through 12 of each 28-day cycle. Treatment continued until disease progression or unacceptable toxicity.


Efficacy was established based on the primary outcome measures of overall survival (OS) and progression-free survival (PFS). Overall survival was statistically significant in patients treated with LONSURF plus bevacizumab compared to those who received LONSURF alone, with a hazard ratio of 0.61 (95% CI: 0.49, 0.77; 1-sided p<0.001). The median OS was 10.8 months vs. 7.5 months in the LONSURF plus bevacizumab arm (95% CI: 9.4, 11.8) and the LONSURF arm (95% CI: 6.3, 8.6), respectively. The median PFS was 5.6 months in the LONSURF plus bevacizumab arm (95% CI: 4.5, 5.9) and 2.4 months in the LONSURF arm (95% CI: 2.1, 3.2) (Hazard ratio 0.44; 95% CI: 0.36, 0.54; 1-sided p<0.001).


The side effects in the experimental arm were neutropenia, anemia, thrombocytopenia, fatigue, nausea, transaminitis, decreased sodium, diarrhea, abdominal pain, and decreased appetite.


In conclusion, the FDA approval of trifluridine and tipiracil (LONSURF) with bevacizumab provides a new treatment option for patients with metastatic colorectal cancer, especially those with specific mutations and prior treatment history. The combination therapy showed significant improvements in overall survival and progression-free survival compared to single-agent LONSURF.

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