Safety of an oral fixed combination of netupitant and palonosetron (NEPA): Pooled data from the phase II/III clinical program

Matti Aapro, Paul J. Hesketh, Karin Jordan, Richard J. Gralla, Giorgia Rossi, Giada Rizzi, Marco Palmas

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background. Standard prophylaxis forchemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a 5-hydroxytryptamine-3 receptor antagonist, a neurokinin-1 receptor antagonist (NK1RA), and corticosteroid therapy. NEPA is a fixed combination of netupitant and palonosetron. The primary objective of this analysis was to document the safety profile, including cardiac safety, of NEPA + dexamethasone in comparison with current therapies across all phase II/III trials. Materials and Methods. This pooled analysis was based on data from 3,280 patients in 4 randomized, double-blind clinical trials. Patients were categorized into 1 of 3 pooled groups on the basis of actual treatment received: NEPA + dexamethasone, palonosetron + dexamethasone, and aprepitant + ondansetron/palonosetron + dexamethasone. Safety was assessed by number and frequency of adverse events (AEs) and changes from baseline electrocardiogram measures. Results. Most patients were female and younger than 65 years of age. Demographic characteristics varied among studies and pooled groups. Frequencies of treatmentemergent AEs (TEAEs) and treatment-related AEs (TRAEs) were similar across groups. TEAEs were mostly mild and consistent with expected chemotherapy and disease-related AEs (hematologic events, hair loss, general weakness). TRAEs in ≥2% of patients were headache and constipation. Frequencies of cardiac TEAEs were similar across groups, with QT prolongation (1.6%), tachycardia (1.1%), and dyspnea (0.9%) the most common. Serious cardiac TEAEs were rare. Conclusion. NEPA was well-tolerated, with an AE profile as expected for the regimen. Sample size, demographic characteristics, study design, chemotherapy, and antiemetic regimen differences across the four studies may have contributed to differences in frequencies of neutropenia and alopecia. Adding an NK1RA to a CINV prophylaxis regimen can improve outcomes without additional toxicity.

Original languageEnglish (US)
Pages (from-to)494-502
Number of pages9
JournalOncologist
Volume21
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Safety
Dexamethasone
Neurokinin-1 Receptor Antagonists
Alopecia
aprepitant
Drug Therapy
Demography
Therapeutics
Receptors, Serotonin, 5-HT3
Ondansetron
Antiemetics
Anthracyclines
Constipation
palonosetron
netupitant
Neutropenia
Tachycardia
Dyspnea
Sample Size
Cyclophosphamide

Keywords

  • Antiemetics
  • Chemotherapy
  • Nausea
  • Neurokinin-1 receptor antagonists
  • Safety
  • Serotonin 5-hydroxytryptamine-3 receptor antagonists
  • Vomiting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Safety of an oral fixed combination of netupitant and palonosetron (NEPA) : Pooled data from the phase II/III clinical program. / Aapro, Matti; Hesketh, Paul J.; Jordan, Karin; Gralla, Richard J.; Rossi, Giorgia; Rizzi, Giada; Palmas, Marco.

In: Oncologist, Vol. 21, No. 4, 01.04.2016, p. 494-502.

Research output: Contribution to journalArticle

Aapro, Matti ; Hesketh, Paul J. ; Jordan, Karin ; Gralla, Richard J. ; Rossi, Giorgia ; Rizzi, Giada ; Palmas, Marco. / Safety of an oral fixed combination of netupitant and palonosetron (NEPA) : Pooled data from the phase II/III clinical program. In: Oncologist. 2016 ; Vol. 21, No. 4. pp. 494-502.
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abstract = "Background. Standard prophylaxis forchemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a 5-hydroxytryptamine-3 receptor antagonist, a neurokinin-1 receptor antagonist (NK1RA), and corticosteroid therapy. NEPA is a fixed combination of netupitant and palonosetron. The primary objective of this analysis was to document the safety profile, including cardiac safety, of NEPA + dexamethasone in comparison with current therapies across all phase II/III trials. Materials and Methods. This pooled analysis was based on data from 3,280 patients in 4 randomized, double-blind clinical trials. Patients were categorized into 1 of 3 pooled groups on the basis of actual treatment received: NEPA + dexamethasone, palonosetron + dexamethasone, and aprepitant + ondansetron/palonosetron + dexamethasone. Safety was assessed by number and frequency of adverse events (AEs) and changes from baseline electrocardiogram measures. Results. Most patients were female and younger than 65 years of age. Demographic characteristics varied among studies and pooled groups. Frequencies of treatmentemergent AEs (TEAEs) and treatment-related AEs (TRAEs) were similar across groups. TEAEs were mostly mild and consistent with expected chemotherapy and disease-related AEs (hematologic events, hair loss, general weakness). TRAEs in ≥2{\%} of patients were headache and constipation. Frequencies of cardiac TEAEs were similar across groups, with QT prolongation (1.6{\%}), tachycardia (1.1{\%}), and dyspnea (0.9{\%}) the most common. Serious cardiac TEAEs were rare. Conclusion. NEPA was well-tolerated, with an AE profile as expected for the regimen. Sample size, demographic characteristics, study design, chemotherapy, and antiemetic regimen differences across the four studies may have contributed to differences in frequencies of neutropenia and alopecia. Adding an NK1RA to a CINV prophylaxis regimen can improve outcomes without additional toxicity.",
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AU - Jordan, Karin

AU - Gralla, Richard J.

AU - Rossi, Giorgia

AU - Rizzi, Giada

AU - Palmas, Marco

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N2 - Background. Standard prophylaxis forchemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a 5-hydroxytryptamine-3 receptor antagonist, a neurokinin-1 receptor antagonist (NK1RA), and corticosteroid therapy. NEPA is a fixed combination of netupitant and palonosetron. The primary objective of this analysis was to document the safety profile, including cardiac safety, of NEPA + dexamethasone in comparison with current therapies across all phase II/III trials. Materials and Methods. This pooled analysis was based on data from 3,280 patients in 4 randomized, double-blind clinical trials. Patients were categorized into 1 of 3 pooled groups on the basis of actual treatment received: NEPA + dexamethasone, palonosetron + dexamethasone, and aprepitant + ondansetron/palonosetron + dexamethasone. Safety was assessed by number and frequency of adverse events (AEs) and changes from baseline electrocardiogram measures. Results. Most patients were female and younger than 65 years of age. Demographic characteristics varied among studies and pooled groups. Frequencies of treatmentemergent AEs (TEAEs) and treatment-related AEs (TRAEs) were similar across groups. TEAEs were mostly mild and consistent with expected chemotherapy and disease-related AEs (hematologic events, hair loss, general weakness). TRAEs in ≥2% of patients were headache and constipation. Frequencies of cardiac TEAEs were similar across groups, with QT prolongation (1.6%), tachycardia (1.1%), and dyspnea (0.9%) the most common. Serious cardiac TEAEs were rare. Conclusion. NEPA was well-tolerated, with an AE profile as expected for the regimen. Sample size, demographic characteristics, study design, chemotherapy, and antiemetic regimen differences across the four studies may have contributed to differences in frequencies of neutropenia and alopecia. Adding an NK1RA to a CINV prophylaxis regimen can improve outcomes without additional toxicity.

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KW - Vomiting

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