Multicycle Efficacy and Safety of Nepa, a Fixed-Dose Antiemetic Combination of Netupitant and Palonosetron, in Patients Receiving Chemotherapy of Varying Emetogenicity

Abstract

ABSTRACT Aim: As emesis is more difficult to suppress once it occurs, preventing chemotherapy-induced nausea and vomiting from the initial cycle through repeated cycles is essential for an optimal patient-centered approach to cancer management. NEPA is a novel, fixed-dose combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA is designed to overcome barriers hindering guideline adherence by targeting two molecular pathways with a single, oral fixed-dose product. NEPA was previously shown to be superior to PALO after a single chemotherapy (CT) cycle; maintenance of efficacy over multiple cycles has been evaluated in a combined dataset from 2 pivotal trials. Methods: These large multinational, randomized studies assessed the efficacy/safety of a single oral dose of NEPA (vs PALO or aprepitant+PALO) in chemotherapy-naive patients receiving multiple cycles of either anthracycline-based (AC) moderately emetogenic CT (MEC) [study 1] or non-AC based MEC or highly emetogenic CT (HEC) [study 2]. All patients also received oral dexamethasone (DEX). Efficacy endpoints were complete response (CR: no emesis, no rescue) and no significant nausea (max Results: 1033 NEPA-treated patients participated in 4428 total cycles in these two trials; 76% completed at least 4 cycles. Overall CR and no significant nausea rates were high and were maintained across 4 cycles of CT with rates being modestly lower in patients receiving AC MEC compared to non-AC MEC and HEC. CR No Significant Nausea (N=AC/non-AC/HEC) AC MEC Non-AC MEC HEC AC MEC Non-AC MEC HEC Cycle 1 (N=724/235/74) 74% 80% 84% 75% 85% 82% Cycle 2 (N=635/212/68) 80% 88% 79% 77% 87% 87% Cycle 3 (N=598/196/63) 84% 91% 91% 78% 89% 92% Cycle 4 (N=551/181/52) 84% 92% 85% 80% 94% 85% The type/incidence of AEs was typical for a diverse cancer population receiving chemotherapy and raised no safety concerns. Conclusions: This is the largest multiple cycle dataset for an antiemetic and provides confidence in the preservation of benefit with NEPA over multiple cycles of AC- and non-AC MEC and HEC. NEPA, a highly convenient, guideline-based antiemetic combination may result in greater adherence and consequently improved emetic control. Disclosure: M.S. Aapro: Consultant, Research Funding, Honoraria: Helsinn Healthcare; R. Gralla: Consultant: Helsinn Healthcare and Eisai Inc.; M. Karthaus: Consultant: Helsinn Healthcare; L. Schwartzberg: Consultant: Helsinn Healthcare & Eisai Inc.; G. Rossi: Employee: Helsinn Healthcare; G. Rizzi: Employee: Helsinn Healthcare; M.E. Borroni: Employee: Helsinn Healthcare; M. Palmas: Employee: Helsinn Heathcare; H.S. Rugo: Consultant and Research Funding: Helsinn Healthcare; K. Jordan: Consultant and Honoraria: Helsinn Healthcare, Merck.