NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron.

Abstract

PURPOSE:

Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study.

METHODS:

This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles.

RESULTS:

Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles.

CONCLUSIONS:

NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

• Authors: Matti Aapro, Meinolf Karthaus, Lee Schwartzberg, Igor Bondarenko, Tomasz Sarosiek, Cristina Oprean, Servando Cardona-Huerta, Vincent Hansen, Giorgia Rossi, Giada Rizzi, Maria Elisa Borroni, Hope Rugo
• Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer (Support Care Cancer) Vol. 25 Issue 4 Pg. 1127-1135 (04 2017) ISSN: 1433-7339 [Electronic] Germany
• PMID: 27885469 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Anthracyclines
• Antiemetics
• Isoquinolines
• Pyridines
• Quinuclidines
• Palonosetron
• netupitant
• Dexamethasone
• Cyclophosphamide

Topics

• Adult
• Anthracyclines (adverse effects)
• Antiemetics (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cyclophosphamide (adverse effects)
• Dexamethasone (administration & dosage)
• Double-Blind Method
• Female
• Humans
• Isoquinolines (administration & dosage)
• Male
• Middle Aged
• Nausea (chemically induced, drug therapy)
• Neoplasms (drug therapy)
• Palonosetron
• Pyridines (administration & dosage)
• Quinuclidines (administration & dosage)
• Vomiting (chemically induced, drug therapy)
• Young Adult