1484PD - Multicycle efficacy and safety of NEPA, a fixed-dose antiemetic combination of netupitant and palonosetron, in patients receiving chemotherapy of v...

Date 29 September 2014
Event ESMO 2014
Session Supportive and palliative care
Topics Supportive Care
Presenter Matti Aapro
Citation Annals of Oncology (2014) 25 (suppl_4): iv517-iv541. 10.1093/annonc/mdu356
Authors M.S. Aapro1, R. Gralla2, M. Karthaus3, L.S. Schwartzberg4, G. Rossi5, G. Rizzi6, M.E. Borroni5, M. Palmas5, H.S. Rugo7, K. Jordan8
  • 1Institut Multidisciplinaire D’oncologie, Clinique de Genolier, 1272 - Genolier/CH
  • 2Medical Oncology, Albert Einstein College of Medicine, Bronx/US
  • 3Oncology, Staedt Klinikum Neuperlach and Harlaching, Munich/DE
  • 4Hematology & Oncology, The West Clinic, Memphis/US
  • 5Corporate Clinical Development, Helsinn Healthcare, Lugano/CH
  • 6Biostatistics & Data Management, Helsinn Healthcare, Lugano/CH
  • 7Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 8Dept. Hematology/ Oncology, University of HalleMartin Luther University Hospital, DE-06120 - Halle/DE

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-naïve 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 <25 mm on 100 mm VAS) during the overall (0-120h) phase.

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.