FDA Approves Lonsurf for Refractory Metastatic Colorectal Cancer

The US Food and Drug Administration (FDA) announced today that it has approved the oral combination therapy Lonsurf (trifluridine plus tipiracil) for patients with refractory advanced colorectal cancer for patients who have been treated previously with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biologic, and an anti-EGFR monoclonal antibody (if RAS wild-type), citing evidence that it can prolong patients’ overall survival (OS) times.¹

“The past decade has brought a new understanding around colorectal cancer, in how we can both detect and treat this often devastating disease,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products, at the FDA Center for Drug Evaluation and Research. “But there are many patients who still need additional options.”²

The drug combines trifluridine, an antineoplastic nucleoside analog, which is incorporated into DNA, thereby interfering with the function of DNA and tipiracil hydrochloride, a thymidine phosphorylase inhibitor that stops tumor enzymes from blocking trifluridine’s anticancer activity.

The recommended dosing schedule is 35 mg/m² orally twice daily within one hour of morning and evening meals on days 1 through 5, and days 8 through 12 of each 28-day cycle, until disease progression or unacceptable toxicity, an FDA advisory stated.

According to findings from an international, randomized, double-blind phase III clinical trial of 800 patients was associated with an average OS of 7.1 months versus 5.3 months for patients receiving placebo (hazard ratio [HR] 0.68; 95% CI: 0.58, 0.81; P < .001). Average progression-free survival (PFS) was 2 months among patients receiving Lonsurf versus 1.7 months for patients administered placebo (HR 0.47; 95% CI: 0.40, 0.55; P < .001).

Side effects included anemia, neutropenia, thrombocytopenia, weakness, fatigue, nausea, decreased appetite, diarrhea, vomiting, abdominal pain, and fever. Women who are breastfeeding should not take Lonsurf. “The FDA recommends that health care providers obtain complete blood counts prior to starting each treatment cycle of Lonsurf and monitor patients throughout treatment, as Lonsurf may cause a severe decrease in blood cell and platelet production (myelosuppression),” the FDA advisory states. “Healthcare providers are also encouraged to advise women of potential risks to developing fetuses when taking Lonsurf.”

Colorectal cancer is the third leading nonskin cancer and the second leading cause of cancer deaths in the United States, according to the National Cancer Institute.

Lonsurf had previously been approved for use in Japan and Otsuka, its manufacturer, submitted the drug for review by regulators in Europe in March 2015.

References:

• U.S. Food and Drug Administration. (2015). Trifluridine/tipiracil.
• U.S. Food and Drug Administration. (2015). FDA approves new oral medication to treat patients with advanced colorectal cancer