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.

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.

• Authors: Shunichi Sugawara, Naoki Inui, Masashi Kanehara, Masahiro Morise, Kozo Yoshimori, Toru Kumagai, Tomoya Fukui, Koichi Minato, Akira Iwashima, Yuichiro Takeda, Kaoru Kubota, Toshiaki Saeki, Tomohide Tamura
• Journal: Cancer (Cancer) Vol. 125 Issue 22 Pg. 4076-4083 (Nov 15 2019) ISSN: 1097-0142 [Electronic] United States
• PMID: 31381152 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Pragmatic Clinical Trial)
• Copyright: © 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Chemical References

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

Topics

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