Randomized, Double-Blind, Phase III Study of Fosnetupitant Versus Fosaprepitant for Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: CONSOLE

J Clin Oncol. 2022 Jan 10;40(2):180-188. doi: 10.1200/JCO.21.01315. Epub 2021 Nov 18.

Abstract

Purpose: We evaluated the efficacy and safety of fosnetupitant (FosNTP) versus fosaprepitant (FosAPR) for preventing highly emetogenic chemotherapy-induced nausea and vomiting. This phase III study was the first head-to-head comparison between two different neurokinin-1 receptor antagonists in combination with palonosetron and dexamethasone.

Patients and methods: Patients scheduled to receive cisplatin-based chemotherapy were randomly assigned 1:1 to FosNTP 235 mg or FosAPR 150 mg in combination with palonosetron 0.75 mg and dexamethasone. The primary end point was overall (0-120 hours) complete response (CR; no emetic event and no rescue medication) rate, stratified by sex and age category, to show the noninferiority of FosNTP to FosAPR (noninferiority margin, -10% for the difference in the overall CR rate).

Results: Overall, 795 patients were randomly assigned, of whom 785 received the study drug (FosNTP [N = 392] v FosAPR [N = 393]) and were evaluated for efficacy and safety. The overall CR rate was 75.2% versus 71.0%, respectively (Mantel-Haenszel common risk difference, 4.1%; 95% CI, -2.1% to 10.3%), demonstrating noninferiority of FosNTP to FosAPR. The CR rates in the acute (0-24 hours), delayed (24-120 hours), and beyond delayed (120-168 hours) phases, and at 0-168 hours were 93.9% versus 92.6%, 76.8% versus 72.8%, 86.5% versus 81.4%, and 73.2% versus 66.9%, respectively. The incidence rates of treatment-related adverse events with FosNTP versus FosAPR were 22.2% versus 25.4%, whereas adverse events or treatment-related adverse events relevant to injection site reactions were 11.0% versus 20.6% (P < .001) and 0.3% versus 3.6% (P < .001), respectively.

Conclusion: FosNTP demonstrated noninferiority to FosAPR, with a favorable safety profile and lower risk for injection site reactions. Thus, FosNTP is valuable in the prophylaxis of acute, delayed, and beyond delayed chemotherapy-induced nausea and vomiting.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Equivalence Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiemetics / adverse effects
  • Antiemetics / therapeutic use*
  • Antineoplastic Agents / adverse effects*
  • Cisplatin / adverse effects*
  • Dexamethasone / therapeutic use
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Isoquinolines / adverse effects
  • Isoquinolines / therapeutic use*
  • Japan
  • Male
  • Middle Aged
  • Morpholines / adverse effects
  • Morpholines / therapeutic use*
  • Nausea / chemically induced
  • Nausea / diagnosis
  • Nausea / prevention & control*
  • Neurokinin-1 Receptor Antagonists / adverse effects
  • Neurokinin-1 Receptor Antagonists / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Quinuclidines / adverse effects
  • Quinuclidines / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Vomiting / chemically induced
  • Vomiting / diagnosis
  • Vomiting / prevention & control*

Substances

  • Antiemetics
  • Antineoplastic Agents
  • Drug Combinations
  • Isoquinolines
  • Morpholines
  • Neurokinin-1 Receptor Antagonists
  • Pyridines
  • Quinuclidines
  • netupitant, palosentron drug combination
  • fosaprepitant
  • Dexamethasone
  • Cisplatin

Associated data

  • JapicCTI/JapicCTI-194611