title: Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy.
abstract: BACKGROUND
  Rolapitant, a novel neurokinin-1 receptor antagonist, provided effective protection against chemotherapy-induced nausea and vomiting (CINV) in a randomized, double-blind phase 3 trial of patients receiving moderately emetogenic chemotherapy or an anthracycline and cyclophosphamide regimen. The current analysis explored the efficacy and safety of rolapitant in preventing CINV in a subgroup of patients receiving carboplatin.
  
  
  METHODS
  Patients were randomized 1:1 to receive oral rolapitant (180 mg) or a placebo 1 to 2 hours before chemotherapy administration; all patients received oral granisetron (2 mg) on days 1 to 3 and oral dexamethasone (20 mg) on day 1. A post hoc analysis examined the subgroup of patients receiving carboplatin in cycle 1. The efficacy endpoints were as follows: complete response (CR), no emesis, no nausea, no significant nausea, complete protection, time to first emesis or use of rescue medication, and no impact on daily life.
  
  
  RESULTS
  In the subgroup administered carboplatin-based chemotherapy (n = 401), a significantly higher proportion of patients in the rolapitant group versus the control group achieved a CR in the overall phase (0-120 hours; 80.2% vs 64.6%; P < .001) and in the delayed phase (>24-120 hours; 82.3% vs 65.6%; P < .001) after chemotherapy administration. Superior responses were also observed by the measures of no emesis, no nausea, and complete protection in the overall and delayed phases and by the time to first emesis or use of rescue medication. The incidence of treatment-emergent adverse events was similar for the rolapitant and control groups.
  
  
  CONCLUSIONS
  Rolapitant provided superior CINV protection to patients receiving carboplatin-based chemotherapy in comparison with the control. These results support rolapitant use as part of the antiemetic regimen in carboplatin-treated patients. Cancer 2016;122:2418-2425. © 2016 American Cancer Society.
authors.affiliation: Department of Hematology and Oncology, Lahey Hospital & Medical Center, Burlington, Massachusetts.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hesketh
authors.affiliation: Compass Oncology, US Oncology Research, Tualatin, Oregon.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Schnadig
authors.affiliation: West Clinic, Memphis, Tennessee.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Schwartzberg
authors.affiliation: Arizona Clinical Research Center and Arizona Oncology, Tucson, Arizona.
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Modiano
authors.affiliation: Hematology and Oncology, Department of Internal Medicine IV, Martin Luther University of Halle-Wittenberg, Halle, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Jordan
authors.affiliation: TESARO, Inc, Waltham, Massachusetts.
authors.forename: Sujata
authors.initials: S
authors.lastname: Arora
authors.affiliation: TESARO, Inc, Waltham, Massachusetts.
authors.forename: Dan
authors.initials: D
authors.lastname: Powers
authors.affiliation: Multidisciplinary Oncology Institute, Clinique de Genolier, Genolier, Switzerland.
authors.forename: Matti
authors.initials: M
authors.lastname: Aapro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018890:Chemoprevention; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D064729:Neurokinin-1 Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D013141:Spiro Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D013141:Spiro Compounds; D016190:Carboplatin; C578834:rolapitant
keywords: carboplatin; chemotherapy-induced nausea and vomiting; moderately emetogenic chemotherapy; neurokinin-1 receptor antagonist; rolapitant