Efficacy benefit of an NK1 receptor antagonist (NK1RA) in patients receiving carboplatin: supportive evidence with NEPA (a fixed combination of the NK1 RA, netupitant, and palonosetron) and aprepitant regimens

Support Care Cancer. 2016 Nov;24(11):4617-25. doi: 10.1007/s00520-016-3304-1. Epub 2016 Jun 22.

Abstract

Purpose: Antiemetic guideline recommendations are inconsistent as to whether a neurokinin-1 receptor antagonist (NK1 RA) should be administered with a 5-hydroxytryptamine-3 (5HT3) RA + dexamethasone (DEX) in patients receiving carboplatin. Patients receiving cisplatin routinely receive an NK1 RA-containing regimen with a resulting 14-22 % benefit in no emesis rates over a 5-HT3 RA/DEX control. Recent studies suggest a similar benefit in patients receiving carboplatin. NEPA is the first fixed antiemetic combination agent and comprises the highly selective NK1 RA, netupitant, and pharmacologically distinct 5-HT3 RA, palonosetron (PALO). This paper presents the efficacy of NEPA in the subset of patients receiving carboplatin in a phase 3 trial (NCT01376297), in the context of aprepitant (APR) data in the carboplatin setting.

Methods: One hundred ninety-six patients (47 % of all study patients: n = 145 NEPA + DEX; n = 51 APR + PALO + DEX) received carboplatin in a multinational, double-blind, randomized phase 3 study. Complete response (CR: no emesis/rescue) and no significant nausea (NSN: score ≤25 on 100 mm visual analog scale) rates were calculated.

Results: Cycle 1-4 overall (0-120 h) CR rates were similar for NEPA (80, 91, 92, and 93 %) and APR (82, 88, 88, and 90 %). Overall NSN rates were also similar (NEPA 84-96 %; APR 82-90 %).

Conclusions: Response rates for NEPA and APR regimens were similar and consistent with prior studies evaluating the contribution of adding NK1 RAs in patients receiving carboplatin. Considering such evidence, guideline groups/practitioners should consider giving a NK1 RA antiemetic triplet in patients receiving carboplatin.

Keywords: Aprepitant; CINV; Carboplatin; NEPA; Netupitant; Palonosetron.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aprepitant
  • Carboplatin / administration & dosage
  • Carboplatin / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Isoquinolines / administration & dosage
  • Isoquinolines / therapeutic use*
  • Male
  • Middle Aged
  • Morpholines / administration & dosage
  • Morpholines / therapeutic use*
  • Palonosetron
  • Pyridines / administration & dosage
  • Pyridines / therapeutic use*
  • Quinuclidines / administration & dosage
  • Quinuclidines / therapeutic use*
  • Receptors, Neurokinin-1 / metabolism*

Substances

  • Isoquinolines
  • Morpholines
  • Pyridines
  • Quinuclidines
  • Receptors, Neurokinin-1
  • Aprepitant
  • Palonosetron
  • netupitant
  • Carboplatin