Efficacy of NEPA, a fixed antiemetic combination of netupitant and palonosetron, vs a 3-day aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese patients receiving highly emetogenic chemotherapy (HEC) in a randomized Phase 3 study

Cancer Med. 2020 Jul;9(14):5134-5142. doi: 10.1002/cam4.3123. Epub 2020 May 30.

Abstract

NEPA is the only fixed combination antiemetic, comprised of an NK1 RA (netupitant) and a 5-HT3 RA (palonosetron). In the first head-to-head trial to compare NK1 RA-containing regimens, a single oral dose of NEPA was non-inferior to a 3-day aprepitant/granisetron (APR/GRAN) regimen for the primary endpoint of overall (0-120 hours) complete response (no emesis/no rescue). This pre-specified analysis evaluates the efficacy of NEPA versus APR/GRAN in the subset of Chinese patients in the study. In addition, efficacy in patients at greatest emetic risk receiving high-dose cisplatin (≥70 mg/m2 ) was explored. Chemotherapy-naïve patients with solid tumors in this randomized, double-blind study received either a single dose of NEPA prior to cisplatin-based chemotherapy or a 3-day regimen of APR/GRAN, both with dexamethasone on Days 1-4. Efficacy was evaluated through complete response, no emesis, and no significant nausea rates during the acute (0-24 hours), delayed (25-120 hours) and overall phases as well as individual days post-chemotherapy, as the daily course of CINV protection is often unstudied. The Chinese subset included 667 patients; of these, 363 (54%) received high-dose cisplatin. Baseline characteristics were comparable. While response rates were similar for NEPA and APR/GRAN during the acute, delayed and overall phases, significantly fewer NEPA patients experienced breakthrough CINV on individual Days 3-5 in both the Chinese patients and also in those receiving high-dose cisplatin. As a fixed oral NK1 RA/5HT3 RA combination given once/cycle, NEPA is a convenient highly effective prophylactic antiemetic that may offer better protection from CINV than a 3-day APR/GRAN regimen on Days 3-5 following highly emetogenic chemotherapy.

Keywords: CINV; NEPA; antiemetic; aprepitant; palonosetron.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiemetics / pharmacology
  • Antiemetics / therapeutic use*
  • Antineoplastic Agents / adverse effects*
  • Aprepitant / pharmacology
  • Aprepitant / therapeutic use*
  • China
  • Double-Blind Method
  • Emetics / pharmacology
  • Emetics / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / drug therapy*
  • Palonosetron / pharmacology
  • Palonosetron / therapeutic use*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Vomiting / chemically induced
  • Vomiting / drug therapy*

Substances

  • Antiemetics
  • Antineoplastic Agents
  • Emetics
  • Pyridines
  • Aprepitant
  • Palonosetron
  • netupitant