FDA Approves Rolapitant for Chemotherapy-Induced Nausea and Vomiting

2015    On September 2, 2015, the US Food and Drug Administration (FDA) approved rolapitant (Varubi™) for the prevention of chemotherapy-induced nausea and vomiting (CINV). Rolapitant, developed by Tesaro, Inc., is a selective and competitive neurokinin 1 (NK-1) receptor antagonist and is relatively long-acting with a half-life of about 7 days). The approval was based on three phase III clinical trials conducted by a research team that included MASCC members Bernardo Rapoport, Martin Chasen, Allen Poma, Lee Schwartzberg, and Rudolph Navari. These randomized, double-blind, controlled trials established the safety and efficacy of rolapitant. The drug was associated with a significant reduction in vomiting and use of rescue antiemetic drugs. Patients treated with rolapitant also reported both fewer episodes of nausea that interfered with their day-to-day life.

Currently, up to 50% of patients undergoing highly or moderately emetogenic chemotherapy experience delayed CINV (25 to 120 hours after chemotherapy), even when taking a 5-HT3 receptor antagonist and corticosteroid. Since rolapitant is neither an inducer nor inhibitor of the metabolic enzyme CYP3A4, it is less likely to interact with other drugs, especially chemotherapy that is metabolized by CYP3A4. Rolapitant is the third NK1 receptor antagonist (after netupitant and aprepitant), a class of drugs important in controlling debilitating nausea and vomiting in chemotherapy patients. The results of the phase III trials were reported at the 2014 MASCC/ISOO Annual Meeting and in the following papers.

Rapoport BL, Chasen MR, Gridelli C, Urban L, Modiano MR, Schnadig ID, Poma A, Arora S, Kansra V, Schwartzberg LS, Navari RM. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials. Lancet Oncol. 2015 Aug 10. [Epub ahead of print]

Schwartzberg LS, Modiano MR, Rapoport BL, Chasen MR, Gridelli C, Urban L, Poma A, Arora S, Navari RM, Schnadig ID. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised, active-controlled, double-blind, phase 3 trial. Lancet Oncol. 2015 Aug 10. [Epub ahead of print]

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