title: A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy.
abstract: BACKGROUND
  Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways.
  
  
  METHODS
  This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve patients receiving moderately emetogenic (anthracycline-cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy end point was complete response (CR: no emesis, no rescue medication) during the delayed (25-120 h) phase in cycle 1.
  
  
  RESULTS
  The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% versus 69.5%; P = 0.001), as were the percentages in the overall (0-120 h) (74.3% versus 66.6%; P = 0.001) and acute (0-24 h) (88.4% versus 85.0%; P = 0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy end points of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO.
  
  
  CONCLUSIONS
  NEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of DEX on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment.
authors.affiliation: Institut Multidisciplinaire d'Oncologie, Clinique de Genolier, Genolier, Switzerland. Electronic address: maapro@genolier.net.
authors.forename: M
authors.initials: M
authors.lastname: Aapro
authors.affiliation: Comprehensive Cancer Center, University of California San Francisco, San Francisco, USA.
authors.forename: H
authors.initials: H
authors.lastname: Rugo
authors.affiliation: Corporate Clinical Development, Statistics and Data Management, Helsinn Healthcare, Lugano, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Corporate Clinical Development, Statistics and Data Management, Helsinn Healthcare, Lugano, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Rizzi
authors.affiliation: Corporate Clinical Development, Statistics and Data Management, Helsinn Healthcare, Lugano, Switzerland.
authors.forename: M E
authors.initials: ME
authors.lastname: Borroni
authors.affiliation: Department of Oncology, Dnepropetrovsk Medical Academy, Dnepropetrovsk, Ukraine.
authors.forename: I
authors.initials: I
authors.lastname: Bondarenko
authors.affiliation: Nzoz Magodent, Warsaw, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Sarosiek
authors.affiliation: Oncomed SRL, Timisoara, Romania.
authors.forename: C
authors.initials: C
authors.lastname: Oprean
authors.affiliation: Hospital Universitario, Universidad Autonoma de Nuevo León, Monterrey, Mexico.
authors.forename: S
authors.initials: S
authors.lastname: Cardona-Huerta
authors.affiliation: National Cancer Institute Giovanni Paolo II, Bari, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.affiliation: Department of Hematology, Oncology and Palliative Medicine, Staedt. Klinikum Neuperlach and Harlaching, München, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Karthaus
authors.affiliation: The West Clinic, Memphis.
authors.forename: L
authors.initials: L
authors.lastname: Schwartzberg
authors.affiliation: Fletcher Allen Health Care, Burlington, USA.
authors.forename: S
authors.initials: S
authors.lastname: Grunberg
mesh_terms: D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D000077924:Palonosetron; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D011812:Quinuclidines / Q000008:administration & dosage* / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*; D010879:Piperazines; D044482:Benzeneacetamides
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D004338:Drug Combinations; D007546:Isoquinolines; D000077924:Palonosetron; D011725:Pyridines; D011812:Quinuclidines; C508854:netupitant; D010879:Piperazines; D044482:Benzeneacetamides
keywords: CINV; NEPA; moderately emetogenic; netupitant; neurokinin-1 receptor antagonist; palonosetron