Efficacy of NEPA (netupitant/palonosetron) across multiple cycles of chemotherapy in breast cancer patients: A subanalysis from two phase III trials.

Abstract

OBJECTIVES:

Breast cancer (BC) patients represent a high-risk population for experiencing chemotherapy-induced nausea and vomiting (CINV), since they frequently receive highly emetogenic anthracycline-cyclophosphamide-based (AC) chemotherapy, and are often female and young, two predisposing risk factors for CINV. Guidelines recommend the combination of a neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine-3 RA (5-HT3RA), and dexamethasone (DEX) for CINV prophylaxis in AC-treated patients. This post-hoc analysis evaluated the efficacy of NEPA, a fixed combination of netupitant (NETU [NK1RA]) and palonosetron (PALO [5-HT3RA]) in BC patients from two phase III studies.

METHODS:

Overall, 1460 BC patients received AC (Study 1) or non-AC (Study 2) therapy over 6060 cycles. Randomized patients received DEX with either NEPA or oral PALO (Study 1), or NEPA or aprepitant+oral PALO (Study 2) before chemotherapy.

RESULTS:

In AC-receiving patients, overall complete response (CR) rates with NEPA+DEX were statistically significantly higher than oral PALO+DEX rates (cycles 1-4: 73.9% vs 65.9%, 80.0% vs 66.0%, 83.6% vs 69.9%, 83.6% vs 74.4%, respectively). Overall, no significant nausea (NSN) rates were also superior with NEPA+DEX vs oral PALO+DEX (respectively, 74.2%-79.9% vs 68.5%-74.9%). A greater proportion of NEPA+DEX patients experienced "no-impact-on-daily-life" due to CINV (78.4% vs 71.4%) in cycle 1. In non-AC-receiving patients, prophylaxis with NEPA+DEX resulted in high CR and NSN rates across 1-4 chemotherapy cycles; no formal comparison with the control arm was performed.

CONCLUSION:

NEPA+DEX administered as a single dose is an effective option for preventing CINV in BC patients receiving AC and non-AC, across multiple chemotherapy cycles.

CLINICAL TRIALS REGISTRATION NUMBERS:

Study 1: NCT01339260, Study 2:NCT01376297.

• Authors: Hope S Rugo, Giorgia Rossi, Giada Rizzi, Matti Aapro
• Journal: Breast (Edinburgh, Scotland) (Breast) Vol. 33 Pg. 76-82 (Jun 2017) ISSN: 1532-3080 [Electronic] Netherlands
• PMID: 28285236 (Publication Type: Journal Article, Meta-Analysis)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Anthracyclines
• Antiemetics
• Drug Combinations
• Isoquinolines
• Pyridines
• Quinuclidines
• netupitant, palosentron drug combination
• Dexamethasone
• Cyclophosphamide

Topics

• Adult
• Aged
• Anthracyclines (adverse effects)
• Antiemetics (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols
• Breast Neoplasms (drug therapy)
• Clinical Trials, Phase III as Topic
• Cyclophosphamide (adverse effects)
• Dexamethasone (administration & dosage)
• Double-Blind Method
• Drug Combinations
• Female
• Humans
• Isoquinolines (administration & dosage)
• Middle Aged
• Nausea (chemically induced, prevention & control)
• Pyridines (administration & dosage)
• Quinuclidines (administration & dosage)
• Treatment Outcome
• Vomiting (chemically induced, prevention & control)
• Young Adult