1765P - Efficacy of intravenous (IV) NEPA, a fixed NK1/5-HT3 receptor antagonist (RA) combination, for prevention of CINV following cisplatin- and anthracycline cyclophosphamide (AC)-based chemotherapy (CT)

Abstract

BackgroundThe antiemetic standard of care recommended by guidelines for prevention of CINV in patients receiving cisplatin- and AC-based CT is the combination of an NK1 RA, a 5-HT3 RA, and dexamethasone (DEX). An IV formulation of NEPA (fixed combination of the NK1 RA, fosnetupitant and 5-HT3 RA, palonosetron) was recently approved in the US and is under review in Europe. Approval of IV NEPA was based on showing pharmacokinetic bioequivalence of IV fosnetupitant to oral netupitant and similar safety of IV NEPA to oral NEPA in a phase III study in patients receiving cisplatin-based CT. An IV/oral NEPA safety-controlled phase IIIb study was recently completed in patients receiving AC CT. In both studies, there were no injection-site or hypersensitivity reactions associated with IV NEPA. This secondary analysis presents the efficacy of IV NEPA relative to that of oral NEPA and other NK1 RAs in cisplatin and AC settings. MethodsData is compiled from 5 pivotal NEPA studies in a total of 2077 adult chemotherapy-naïve patients with solid tumors undergoing either cisplatin- or AC-based CT. IV NEPA was administered as a single 30-min infusion; oral NEPA was given as a single capsule 60min prior to CT. Patients also received DEX. Data was also reviewed from 9 phase III cisplatin and AC studies with other NK1 RA (aprepitant [APR], fosaprepitant [FOS], rolapitant [ROL]) regimens. No emesis rates are summarized for the overall phase (0-120h) of the initial cycle of CT. No formal statistical comparisons were performed. ResultsThe overall no emesis rates of>80% for IV NEPA were similar to oral NEPA in both cisplatin and AC settings and were favorable in the context of historical NK1 RA regimens.Table1765PTableSetting/StudyIV NEPA + DEXOral NEPA + DEXAPR + 5-HT3RA + DEXFOS + 5-HT3RA + DEXROL + 5-HT3RA + DEXCisplatinSchwartzberg 201884.2%88.6%--Hesketh 2014-91.1%--Zhang 2018-75.0%--Grunberg 2011--74.6%72.9%Hesketh 2003--77.7%--Poli-Bigelli 2003--66%--Schmoll 2006--76.5%--Saito 2013---67.6%-Rapoport 2015 (HEC-1)----75%Rapoport 2015 (HEC-2)----71%ACSchwartzberg 201982.5%86.1%---Aapro 2014-79.8%---Warr 2005--76%--Schwartzberg 2016----72.4% ConclusionsBoth IV and oral formulations of NEPA along with DEX represent highly effective guideline-compliant single-dose antiemetics. Clinical trial identificationNCT03403712. Editorial acknowledgementJennifer Vanden Burgt, Minneapolis, MN, funded by Helsinn Healthcare, Lugano, Switzerland. Legal entity responsible for the studyHelsinn Healthcare. FundingHelsinn Healthcare. DisclosureL. Schwartzberg: Advisory / Consultancy, Research grant / Funding (institution): Helsinn Healthcare ; Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Advisory / Consultancy: Merck ; Advisory / Consultancy: Heron. M.S. Aapro: Advisory / Consultancy, Research grant / Funding (institution): Helsinn Healthcare; Advisory / Consultancy: Mundipharma; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Merck; Advisory / Consultancy: G1 Therapeutics.