NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting (CINV) following repeated chemotherapy cycles: Results of a phase III trial.

Abstract

e20716 Background: NEPA is a fixed-dose combination of netupitant (NETU), a highly selective NK1 receptor antagonist and palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3receptor antagonist. Recent clinical trials have been conducted to definitively establish the superiority of the combination, NEPA, over single agent PALO in the prevention of CINV following a single cycle of highly (HEC) and moderately (MEC) emetogenic CT. This study was designed to examine the tolerability and efficacy of NEPA over multiple cycles of HEC and MEC. Methods: Trial design: multinational, randomized, double-blind, parallel group, phase III study assessing the safety and efficacy of a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) administered only on day 1 of each cycle, and given with concomitant oral dexamethasone on day 1 (with MEC) and days 1-4 (when given with HEC) prior to repeated cycles of HEC or MEC. A standard arm 3-day oral aprepitant + PALO + dexamethasone was included as a control group with an unbalanced 3:1 (NEPA : aprepitant) randomization ratio. There was no limit to the number of chemotherapy cycles allowed. Safety was the primary objective of the study as assessed by adverse events; secondary variables included ECGs, left ventricular ejection fraction, cardiac troponin levels and laboratory tests. Efficacy was assessed as the proportion of patients with complete response (no emesis, no rescue medication). Results: 413 patients were randomized in this study with the last patient visit occurring on 13 September, 2012. The analyses will be completed by March 2013 and will be fully available by ASCO 2013. Conclusions: Few large randomized trials have documented safety and efficacy of antiemetic control with multiple cycles of chemotherapy, and especially with HEC. The in depth safety profile will provide new information for all study arms over multiple cycles. NEPA is designed to provide maximal convenience while providing high degrees of antiemetic control throughout the patient’s full course of chemotherapy. Clinical trial information: NCT01376297.