Multicenter, placebo-controlled, double-blind, randomized study of fosnetupitant in combination with palonosetron for the prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy

Cancer. 2019 Nov 15;125(22):4076-4083. doi: 10.1002/cncr.32429. Epub 2019 Aug 5.

Abstract

Background: The current randomized, double-blind, phase 2 study assessed the efficacy and safety profile of a single intravenous administration of fosnetupitant, a neurokinin 1 receptor antagonist prodrug, for the prevention of chemotherapy-induced nausea and vomiting in Japanese patients receiving cisplatin-based chemotherapy.

Methods: Patients scheduled to receive cisplatin (at a dose of ≥70 mg/m2 )-based regimens were randomly assigned to receive fosnetupitant at a dose of 81 mg or 235 mg or placebo in combination with palonosetron at a dose of 0.75 mg and dexamethasone. The primary endpoint was complete response (CR; no vomiting and no rescue medication) during the overall phase (0-120 hours). The overall CR rate was compared between each dose of fosnetupitant and the placebo group adjusting for the stratification factors of sex and age class (age <55 years vs age ≥55 years). Safety was assessed, with special attention given to events that potentially were suggestive of infusion site reactions.

Results: A total of 594 patients were randomized. Of these, 194 patients, 195 patients, and 195 patients, respectively, in the placebo and fosnetupitant 81-mg and 235-mg dose groups were evaluable for efficacy. The overall CR rate was 54.7% for the placebo group, 63.8% for the fosnetupitant 81-mg dose group (adjusted difference, 9.1%; 95% CI, -0.4% to 18.6% [P = .061]), and 76.8% for the fosnetupitant 235-mg dose group (adjusted difference, 22.0%; 97.5% CI, 11.7% to 32.3% [P < .001]). Safety profiles were comparable between the 3 groups. The incidence of infusion site reactions related to fosnetupitant was ≤1% in each dose group.

Conclusions: Fosnetupitant at a dose of 235 mg provided superior prevention of chemotherapy-induced nausea and vomiting among patients receiving cisplatin-based chemotherapy compared with the control group, and with a satisfactory safety profile.

Keywords: chemotherapy-induced nausea and vomiting; fosnetupitant; highly emetogenic chemotherapy; injection site reaction; neurokinin 1 receptor antagonist; phase 2.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Pragmatic Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antiemetics / administration & dosage
  • Antiemetics / pharmacokinetics
  • Antiemetics / therapeutic use*
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Drug Combinations
  • Female
  • Humans
  • Isoquinolines / administration & dosage
  • Isoquinolines / pharmacokinetics
  • Isoquinolines / therapeutic use*
  • Male
  • Middle Aged
  • Nausea / etiology*
  • Nausea / prevention & control*
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Pyridines / administration & dosage
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use*
  • Quinuclidines / administration & dosage
  • Quinuclidines / pharmacokinetics
  • Quinuclidines / therapeutic use*
  • Treatment Outcome
  • Vomiting / etiology*
  • Vomiting / prevention & control*

Substances

  • Antiemetics
  • Antineoplastic Agents
  • Drug Combinations
  • Isoquinolines
  • Pyridines
  • Quinuclidines
  • netupitant, palosentron drug combination

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