Lonsurf Plus Bevacizumab Approved for Metastatic Colorectal Cancer

The Food and Drug Administration (FDA) has approved Lonsurf^® (trifluridine/tipiracil) in combination with bevacizumab for the treatment of adults with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. Previously, Lonsurf was approved only as a single agent for this indication.

The approval was based on data from the phase 3 SUNLIGHT trial (ClinicalTrials.gov Identifier: NCT04737187), which compared the efficacy and safety of Lonsurf with bevacizumab (n=246) to Lonsurf as a single agent (n=246) in adults with mCRC who received a maximum of 2 prior chemotherapy regimens and demonstrated progressive disease or intolerance to the last regimen. The primary endpoint was overall survival (OS).

Median OS was reported to be 10.8 months in the Lonsurf plus bevacizumab arm compared with 7.5 months in the Lonsurf monotherapy arm (hazard ratio [HR], 0.61; 95% CI, 0.49-0.77; 1-sided P <.001). Median progression free survival (secondary endpoint) was 5.6 months in the Lonsurf plus bevacizumab arm vs 2.4 months in the Lonsurf monotherapy arm (HR, 0.44; 95% CI, 0.36-0.54; 1-sided P <.001).

The most common adverse reactions with the combination were neutropenia, anemia, thrombocytopenia, fatigue, nausea, increased AST, increased ALT, increased alkaline phosphatase, decreased sodium, diarrhea, abdominal pain, and decreased appetite.

“The FDA approval of this combination provides patients with mCRC 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 pivotal phase 3 SUNLIGHT trial that evaluated this combination. “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.”

Lonsurf is also approved for the treatment of adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least 2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.