The FDA has approved Lonsurf (Taiho Oncology), a combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil, for oral treatment of metastatic colorectal cancer. Trifluridine is incorporated into DNA, interfering with DNA synthesis and inhibiting cell proliferation. Tipiracil inhibits the metabolism of trifluridine. The combination is only approved for use in patients who were previously treated with a fluoropyrimidine (fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-VEGF biological such as bevacizumab, and, if the tumor is RAS wild-type, an anti-EGFR agent (cetuximab or panitumumab). The median survival of patients with metastatic colorectal cancer treated with these drugs is about 30 months.

FDA approval of trifluridine/tipiracil was based on the results of a randomized, double-blind, placebo-controlled trial in 800 patients with metastatic colorectal cancer who had previously been treated with chemotherapy and biological therapy. Median overall survival, the primary endpoint, was significantly longer with trifluridine/tipiracil compared to placebo (7.1 months vs 5.3 months). Median progression-free survival, a secondary endpoint, was 1.7 months with placebo and 2.0 months with trifluridine/tipiracil. The most common adverse effects of the combination included nausea, vomiting, diarrhea, fatigue, neutropenia, anemia, and leukopenia. Among 533 patients treated with the combination, only one treatment-related death occurred (from septic shock).1

Lonsurf is available in tablets containing 15 mg of trifluridine and 6.14 mg of tipiracil or 20 mg of trifluridine and 8.19 mg of tipiracil. The recommended dosage is 35 mg/m² (based on the trifluridine component) orally twice daily on days 1-5 and 8-12 of each 28-day cycle until disease progression or unacceptable toxicity occurs. Lonsurf should be taken within one hour after meals. The cost of one treatment cycle (sixty 20 mg/8.19 mg tablets) is $10,947.70.2

1. RJ Mayer et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med 2015; 372:1909.
2. Approximate WAC for a patient with a 1.7 m² surface area. WAC = wholesaler acquisition cost or manufacturer's published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. May 5, 2016. Reprinted with permission by First Databank, Inc. All rights reserved. ©2016. www.fdbhealth. com/policies/drug-pricing-policy.

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The FDA has approved Akynzeo (Helsinn/Eisai), an oral fixed-dose combination of the substance P/neurokinin 1 (NK₁) receptor antagonist netupitant and the serotonin-3 (5-HT₃) receptor antagonist palonosetron, for prevention of acute and delayed nausea and vomiting associated with cancer chemotherapy in adults. Akynzeo is the first product to combine drugs from these two classes. Palonosetron (Aloxi) is also available as a single agent for prevention of chemotherapy-induced and postoperative nausea and vomiting. Netupitant is the second substance P/NK₁ receptor antagonist to be approved in the US; aprepitant (Emend) was the first.

Panitumumab (Vectibix - Amgen), a fully human IgG₂ monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR), has been approved by the FDA for treatment of patients with EGFR-expressing metastatic colorectal cancer that has progressed despite standard chemotherapy. It is the second monoclonal antibody EGFR inhibitor to be approved for metastatic colorectal cancer; cetuximab (Erbitux), a human-murine chimeric IgG₁ monoclonal antibody, was approved in 2004.