Rolapitant-Based Antiemetic Combination Improves CINV Symptoms

Adding rolapitant (180 mg) to a serotonin-3 (5-HT3) receptor antagonist and dexamethasone is well tolerated and more effectively controls chemotherapy-induced nausea and vomiting (CINV) compared with 5-HT3 receptor antagonist and dexamethasone alone, according to a meta-analysis of safety and efficacy data pooled from five randomized controlled trials representing 2,984 patients, 1,438 of whom were assigned to receive rolapitant-based therapy. The findings were published in Current Problems in Cancer.

CINV is a widespread and debilitating side effect of anticancer chemotherapy. Rolapitant is a novel, U.S. Food and Drug Administration (FDA)–approved selective neurokinin-1 (NK-1) receptor antagonist. NK-1 receptor antagonists inhibit substance P-mediated receptor activity in the brainstem and abdominal vagus nerve, short-circuiting vomit-reflex signaling. Aprepitant, fosaprepitant, and netupitant are other agents in this class.

The analysis included data from five studies described in four published papers.[1-4] The meta-analytic acute (first 5 days) and delayed antiemetic complete response rates were superior for rolapitant (acute efficacy odds ratio [OR], 1.4; 95% CI: 1.16-1.7; delayed efficacy OR, 1.68; 95% CI: 1.44-1.96). Complete protection rates were significantly improved with rolapitant over placebo overall (OR, 1.52; 95% CI: 1.3-1.76).

Unplanned hospital admission and patient-reported quality-of-life outcomes were not “adequately investigated” in the studied clinical trials, the authors noted. Nor have head-to-head comparative clinical trials assessed the relative benefits of the available NK-1 antagonists for CINV prevention.

The FDA has approved rolapitant for use in combination with a 5-HT3 receptor antagonist and dexamethasone.

The authors did not disclose funding sources or disclose potential conflicts of interest for the meta-analysis.

References:

1. Schwartzberg LS, Modiano MR, Rapoport BL, et al. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised, active-control. The Lancet Oncology. 2015;16:1071-8.

2. Rapoport BL, Chasen ML, Gridelli C, et al. 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-controled, double-blind, phase 3 trials. The Lancet Oncology. 2015;16:1079-89.

3. Rapoport B Study of rolapitant, a novel, long-acting, NK-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). Supportive Care in Cancer. 2015;23:3281-8.

4. Hesketh, PJ, Schnadig ID, Schwartzberg LS, et al. Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy. Cancer. 2016;122:2418-25.