Evidence map›Paper›PMID 24608196›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2014

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.

P J Hesketh, G Rossi, G Rizzi, M Palmas, A Alyasova, I Bondarenko, A Lisyanskaya, R J Gralla

Open access · bronzeAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 13 pooled it
27.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

106 citing papers in PubMed, 13 syntheses or guidelines pooled it, 220 citations in OpenAlex.

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  4. Interventions for the prevention of acute phase chemotherapy-induced nausea and vomiting in adult and pediatric patients: a systematic review and meta-analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022
    Pooled it
  5. SEOM clinical guideline emesis (2021).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
    Guideline
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  12. 2016 Updated MASCC/ESMO Consensus Recommendations: Prevention of Nausea and Vomiting Following High Emetic Risk Chemotherapy.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2017
    Pooled it
  13. Defining the efficacy of neurokinin-1 receptor antagonists in controlling chemotherapy-induced nausea and vomiting in different emetogenic settings-a meta-analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2016
    Pooled it
  14. A phase 2 pharmacokinetic and pharmacodynamic dose-finding study of oral NEPA for chemotherapy-induced nausea and vomiting in pediatric patients with cancer.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
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46 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 6 institutions in 4 countries.

P J HeskethLahey Hospital & Medical Center, Burlington, USA. Electronic address: paul.hesketh@lahey.org.
G RossiCorporate Clinical Development and Statistics & Data Management, Helsinn Healthcare SA, Lugano, Switzerland.
G RizziCorporate Clinical Development and Statistics & Data Management, Helsinn Healthcare SA, Lugano, Switzerland.
M PalmasCorporate Clinical Development and Statistics & Data Management, Helsinn Healthcare SA, Lugano, Switzerland.
A AlyasovaFederal State Institution, Privolzhsky District Medical Center under the Federal Medical-Biological Agency of Russia, Nizhny Novgorod, Russia.
I BondarenkoDnepropetrovsk Medical Academy, Dnepropetrovsk, Ukraine.
A LisyanskayaCity Clinical Oncology Dispensary, Saint Petersburg, Russia.
R J GrallaAlbert Einstein College of Medicine, Bronx, USA.
Helsinn (Switzerland) · CHAlbert Einstein College of Medicine · USCity Clinical Oncology Center · RUDnipropetrovsk State Medical Academy · UAFederal Medical-Biological Agency · RULahey Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNEPA 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

methodsThis 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.

resultsAll 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.

conclusionsEach 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.

Indexed as

Administration, OralAntineoplastic AgentsBenzeneacetamidesDose-Response Relationship, DrugDouble-Blind MethodDrug CombinationsFemaleHumansIsoquinolinesMaleMiddle AgedNauseaPalonosetronPiperazinesPyridinesQuinuclidinesAntineoplastic AgentsBenzeneacetamidesDrug CombinationsIsoquinolinesnetupitantPalonosetronPiperazinesPyridinesQuinuclidinesCINVhighly emetogenicNEPAnetupitantneurokinin-1 receptor antagonistpalonosetron

Identifiers

PMID24608196
PMCPMC4071755
OpenAlexW2162984217

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.