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Ann Oncol. 2014 Jul;25(7):1340-6. doi: 10.1093/annonc/mdu110. Epub 2014 Mar 7.

Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study.

Author information

1
Lahey Hospital & Medical Center, Burlington, USA paul.hesketh@lahey.org.
2
Corporate Clinical Development and Statistics & Data Management, Helsinn Healthcare SA, Lugano, Switzerland.
3
Federal State Institution, Privolzhsky District Medical Center under the Federal Medical-Biological Agency of Russia, Nizhny Novgorod, Russia.
4
Dnepropetrovsk Medical Academy, Dnepropetrovsk, Ukraine.
5
City Clinical Oncology Dispensary, Saint Petersburg, Russia.
6
Albert Einstein College of Medicine, Bronx, USA.

Abstract

BACKGROUND:

NEPA is a novel oral fixed-dose combination of netupitant (NETU), a new highly selective neurokinin-1 (NK1) receptor antagonist (RA) and palonosetron (PALO), a pharmacologically and clinically distinct 5-hydroxytryptamine type 3 (5-HT3) RA. This study was designed to determine the appropriate clinical dose of NETU to combine with PALO for evaluation in the phase 3 NEPA program.

PATIENTS AND METHODS:

This randomized, double-blind, parallel group study in 694 chemotherapy naïve patients undergoing cisplatin-based chemotherapy for solid tumors compared three different oral doses of NETU (100, 200, and 300 mg) + PALO 0.50 mg with oral PALO 0.50 mg, all given on day 1. A standard 3-day aprepitant (APR) + IV ondansetron (OND) 32 mg regimen was included as an exploratory arm. All patients received oral dexamethasone on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the overall (0-120 h) phase.

RESULTS:

All NEPA doses showed superior overall CR rates compared with PALO (87.4%, 87.6%, and 89.6% for NEPA100, NEPA200, and NEPA300, respectively versus 76.5% PALO; P < 0.050) with the highest NEPA300 dose studied showing an incremental benefit over lower NEPA doses for all efficacy endpoints. NEPA300 was significantly more effective than PALO and numerically better than APR + OND for all secondary efficacy endpoints of no emesis, no significant nausea, and complete protection (CR plus no significant nausea) rates during the acute (0-24 h), delayed (25-120 h), and overall phases. Adverse events were comparable across groups with no dose response. The percent of patients developing electrocardiogram changes was also comparable.

CONCLUSIONS:

Each NEPA dose provided superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with PALO following highly emetogenic chemotherapy; however, NEPA300 was the best dose studied, with an advantage over lower doses for all efficacy endpoints. The combination of NETU and PALO was well tolerated with a similar safety profile to PALO and APR + OND.

KEYWORDS:

CINV; NEPA; highly emetogenic; netupitant; neurokinin-1 receptor antagonist; palonosetron

PMID:
24608196
PMCID:
PMC4071755
DOI:
10.1093/annonc/mdu110
[Indexed for MEDLINE]
Free PMC Article

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