Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy

Cancer. 2016 Aug 1;122(15):2418-25. doi: 10.1002/cncr.30054. Epub 2016 May 13.

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.

Keywords: carboplatin; chemotherapy-induced nausea and vomiting; moderately emetogenic chemotherapy; neurokinin-1 receptor antagonist; rolapitant.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Chemoprevention
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / drug therapy*
  • Nausea / etiology*
  • Nausea / prevention & control
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Neoplasms / mortality
  • Neurokinin-1 Receptor Antagonists / adverse effects
  • Neurokinin-1 Receptor Antagonists / therapeutic use*
  • Risk Factors
  • Spiro Compounds / adverse effects
  • Spiro Compounds / therapeutic use*
  • Treatment Outcome
  • Vomiting / drug therapy*
  • Vomiting / etiology*
  • Vomiting / prevention & control

Substances

  • Neurokinin-1 Receptor Antagonists
  • Spiro Compounds
  • Carboplatin
  • rolapitant