title: 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: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3RA. 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.
authors.affiliation: Clinique de Genolier, Institut Multidisciplinaire d'Oncologie, Case Postale (P.O. Box) 100, Route du Muids 3, 1272, Genolier, Switzerland. maapro@genolier.net.
authors.forename: Matti
authors.initials: M
authors.lastname: Aapro
authors.affiliation: Hematology and Oncology, Staedt Klinikum Neuperlach and Harlaching, Munich, Germany.
authors.forename: Meinolf
authors.initials: M
authors.lastname: Karthaus
authors.affiliation: The West Clinic, Memphis,, TN, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Schwartzberg
authors.affiliation: Dnepropetrovsk Medical Academy, Dnepropetrovsk, Ukraine.
authors.forename: Igor
authors.initials: I
authors.lastname: Bondarenko
authors.affiliation: NZOZ Magodent, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sarosiek
authors.affiliation: Oncomed SRL, Timisoara, Romania.
authors.forename: Cristina
authors.initials: C
authors.lastname: Oprean
authors.affiliation: Universidad Autonoma de Nuevo Leon, Monterrey, Mexico.
authors.forename: Servando
authors.initials: S
authors.lastname: Cardona-Huerta
authors.affiliation: Northern Utah Associates, Ogden,, UT, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Hansen
authors.affiliation: Helsinn Healthcare SA, Lugano, Switzerland.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Helsinn Healthcare SA, Lugano, Switzerland.
authors.forename: Giada
authors.initials: G
authors.lastname: Rizzi
authors.affiliation: Helsinn Healthcare SA, Lugano, Switzerland.
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Borroni
authors.affiliation: Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Hope
authors.initials: H
authors.lastname: Rugo
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects; D000932:Antiemetics / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy; D000077924:Palonosetron; D011725:Pyridines / Q000008:administration & dosage*; D011812:Quinuclidines / Q000008:administration & dosage*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*; D055815:Young Adult; D010879:Piperazines; D044482:Benzeneacetamides
chemical_list: D018943:Anthracyclines; D000932:Antiemetics; D003520:Cyclophosphamide; D003907:Dexamethasone; D007546:Isoquinolines; D000077924:Palonosetron; D011725:Pyridines; D011812:Quinuclidines; C508854:netupitant; D010879:Piperazines; D044482:Benzeneacetamides
keywords: CINV; Multiple cycles; NEPA; Netupitant; Neurokinin-1 receptor antagonist; Palonosetron