title: Efficacy of NEPA (netupitant/palonosetron) across multiple cycles of chemotherapy in breast cancer patients: A subanalysis from two phase III trials.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
  Study 1: NCT01339260, Study 2:NCT01376297.
authors.affiliation: University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, 94115, USA. Electronic address: Hope.Rugo@ucsf.edu.
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.affiliation: Helsinn Healthcare SA, 6912, Pazzallo, Lugano, Switzerland.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Helsinn Healthcare SA, 6912, Pazzallo, Lugano, Switzerland.
authors.forename: Giada
authors.initials: G
authors.lastname: Rizzi
authors.affiliation: IMO Clinique de Genolier, CH-1272, Genolier, Vaud, Switzerland.
authors.forename: Matti
authors.initials: M
authors.lastname: Aapro
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects; D000932:Antiemetics / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D003520:Cyclophosphamide / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D011725:Pyridines / Q000008:administration & dosage*; D011812:Quinuclidines / Q000008:administration & dosage*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000932:Antiemetics; D004338:Drug Combinations; D007546:Isoquinolines; D011725:Pyridines; D011812:Quinuclidines; C000595957:netupitant, palosentron drug combination; D003907:Dexamethasone; D003520:Cyclophosphamide
keywords: Antiemetic; Breast cancer; CINV; NEPA; Netupitant; Palonosetron