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Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy‐Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy
BACKGROUND: NEPA, a combination antiemetic of a neurokinin‐1 (NK(1)) receptor antagonist (RA) (netupitant [oral]/fosnetupitant [intravenous; IV]) and 5‐HT(3)RA, palonosetron] offers 5‐day CINV prevention with a single dose. Fosnetupitant solution contains no allergenic excipients, surfactant, emulsi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066686/ https://www.ncbi.nlm.nih.gov/pubmed/32162813 http://dx.doi.org/10.1634/theoncologist.2019-0527 |
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author | Schwartzberg, Lee Navari, Rudolph Clark‐Snow, Rebecca Arkania, Ekaterine Radyukova, Irena Patel, Kamal Voisin, Daniel Rizzi, Giada Wickham, Rita Gralla, Richard J. Aapro, Matti Roeland, Eric |
author_facet | Schwartzberg, Lee Navari, Rudolph Clark‐Snow, Rebecca Arkania, Ekaterine Radyukova, Irena Patel, Kamal Voisin, Daniel Rizzi, Giada Wickham, Rita Gralla, Richard J. Aapro, Matti Roeland, Eric |
author_sort | Schwartzberg, Lee |
collection | PubMed |
description | BACKGROUND: NEPA, a combination antiemetic of a neurokinin‐1 (NK(1)) receptor antagonist (RA) (netupitant [oral]/fosnetupitant [intravenous; IV]) and 5‐HT(3)RA, palonosetron] offers 5‐day CINV prevention with a single dose. Fosnetupitant solution contains no allergenic excipients, surfactant, emulsifier, or solubility enhancer. A phase III study of patients receiving cisplatin found no infusion‐site or anaphylactic reactions related to IV NEPA. However, hypersensitivity reactions and anaphylaxis have been reported with other IV NK(1)RAs, particularly fosaprepitant in patients receiving anthracycline‐cyclophosphamide (AC)‐based chemotherapy. This study evaluated the safety and efficacy of IV NEPA in the AC setting. MATERIALS AND METHODS: This phase IIIb, multinational, randomized, double‐blind study enrolled females with breast cancer naive to highly or moderately emetogenic chemotherapy. Patients were randomized to receive a single 30‐minute infusion of IV NEPA or single oral NEPA capsule on day 1 prior to AC, in repeated (up to 4) cycles. Oral dexamethasone was given to all patients on day 1 only. RESULTS: A total of 402 patients were included. The adverse event (AE) profiles were similar for IV and oral NEPA and consistent with those expected. Most AEs were mild or moderate with a similarly low incidence of treatment‐related AEs in both groups. There were no treatment‐related injection‐site AEs and no reports of hypersensitivity or anaphylaxis. The efficacy of IV and oral NEPA were similar, with high complete response (no emesis/no rescue) rates observed in cycle 1 (overall [0–120 hours] 73.0% IV NEPA, 77.3% oral NEPA) and maintained over subsequent cycles. CONCLUSION: IV NEPA was highly effective and safe with no associated hypersensitivity and injection‐site reactions in patients receiving AC. IMPLICATIONS FOR PRACTICE: As a combination of a neurokinin‐1 (NK(1)) receptor antagonist (RA) and 5‐HT(3)RA, NEPA offers 5‐day chemotherapy‐induced nausea and vomiting prevention with a single dose and an opportunity to improve adherence to antiemetic guidelines. In this randomized multinational phase IIIb study, intravenous (IV) NEPA (fosnetupitant/palonosetron) was safe and highly effective in patients receiving multiple cycles of anthracycline‐cyclophosphamide (AC)‐based chemotherapy. Unlike other IV NK(1)RAs, the IV NEPA combination solution does not require any surfactant, emulsifier, or solubility enhancer and contains no allergenic excipients. Hypersensitivity reactions and anaphylaxis have been reported with other IV NK(1)RAs, most commonly with fosaprepitant in the AC setting. Importantly, there were no injection‐site or hypersensitivity reactions associated with IV NEPA. |
format | Online Article Text |
id | pubmed-7066686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70666862020-04-06 Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy‐Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy Schwartzberg, Lee Navari, Rudolph Clark‐Snow, Rebecca Arkania, Ekaterine Radyukova, Irena Patel, Kamal Voisin, Daniel Rizzi, Giada Wickham, Rita Gralla, Richard J. Aapro, Matti Roeland, Eric Oncologist Symptom Management and Supportive Care BACKGROUND: NEPA, a combination antiemetic of a neurokinin‐1 (NK(1)) receptor antagonist (RA) (netupitant [oral]/fosnetupitant [intravenous; IV]) and 5‐HT(3)RA, palonosetron] offers 5‐day CINV prevention with a single dose. Fosnetupitant solution contains no allergenic excipients, surfactant, emulsifier, or solubility enhancer. A phase III study of patients receiving cisplatin found no infusion‐site or anaphylactic reactions related to IV NEPA. However, hypersensitivity reactions and anaphylaxis have been reported with other IV NK(1)RAs, particularly fosaprepitant in patients receiving anthracycline‐cyclophosphamide (AC)‐based chemotherapy. This study evaluated the safety and efficacy of IV NEPA in the AC setting. MATERIALS AND METHODS: This phase IIIb, multinational, randomized, double‐blind study enrolled females with breast cancer naive to highly or moderately emetogenic chemotherapy. Patients were randomized to receive a single 30‐minute infusion of IV NEPA or single oral NEPA capsule on day 1 prior to AC, in repeated (up to 4) cycles. Oral dexamethasone was given to all patients on day 1 only. RESULTS: A total of 402 patients were included. The adverse event (AE) profiles were similar for IV and oral NEPA and consistent with those expected. Most AEs were mild or moderate with a similarly low incidence of treatment‐related AEs in both groups. There were no treatment‐related injection‐site AEs and no reports of hypersensitivity or anaphylaxis. The efficacy of IV and oral NEPA were similar, with high complete response (no emesis/no rescue) rates observed in cycle 1 (overall [0–120 hours] 73.0% IV NEPA, 77.3% oral NEPA) and maintained over subsequent cycles. CONCLUSION: IV NEPA was highly effective and safe with no associated hypersensitivity and injection‐site reactions in patients receiving AC. IMPLICATIONS FOR PRACTICE: As a combination of a neurokinin‐1 (NK(1)) receptor antagonist (RA) and 5‐HT(3)RA, NEPA offers 5‐day chemotherapy‐induced nausea and vomiting prevention with a single dose and an opportunity to improve adherence to antiemetic guidelines. In this randomized multinational phase IIIb study, intravenous (IV) NEPA (fosnetupitant/palonosetron) was safe and highly effective in patients receiving multiple cycles of anthracycline‐cyclophosphamide (AC)‐based chemotherapy. Unlike other IV NK(1)RAs, the IV NEPA combination solution does not require any surfactant, emulsifier, or solubility enhancer and contains no allergenic excipients. Hypersensitivity reactions and anaphylaxis have been reported with other IV NK(1)RAs, most commonly with fosaprepitant in the AC setting. Importantly, there were no injection‐site or hypersensitivity reactions associated with IV NEPA. John Wiley & Sons, Inc. 2019-12-08 2020-03 /pmc/articles/PMC7066686/ /pubmed/32162813 http://dx.doi.org/10.1634/theoncologist.2019-0527 Text en © 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Symptom Management and Supportive Care Schwartzberg, Lee Navari, Rudolph Clark‐Snow, Rebecca Arkania, Ekaterine Radyukova, Irena Patel, Kamal Voisin, Daniel Rizzi, Giada Wickham, Rita Gralla, Richard J. Aapro, Matti Roeland, Eric Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy‐Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy |
title | Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy‐Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy |
title_full | Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy‐Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy |
title_fullStr | Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy‐Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy |
title_full_unstemmed | Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy‐Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy |
title_short | Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy‐Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy |
title_sort | phase iiib safety and efficacy of intravenous nepa for prevention of chemotherapy‐induced nausea and vomiting (cinv) in patients with breast cancer receiving initial and repeat cycles of anthracycline and cyclophosphamide (ac) chemotherapy |
topic | Symptom Management and Supportive Care |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066686/ https://www.ncbi.nlm.nih.gov/pubmed/32162813 http://dx.doi.org/10.1634/theoncologist.2019-0527 |
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