Olanzapine With or Without Fosaprepitant for Preventing Chemotherapy Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Phase III Randomized, Double-Blind, Placebo-Controlled Trial (ALLIANCE A221602)

by Selleckchem | Oct 04 2023

Purpose: A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an olanzapine-based antiemetogenic regimen was used.

Materials and methods: A221602, a prospective double-blind, placebo-controlled clinical trial, was developed to compare 2 -olanzapine-containing antiemetic regimens, one with an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Trial patients had a malignant disease for which they received intravenous highly emetogenic chemotherapy (single day cisplatin ≥ 70 mg/m2 or doxorubicin plus cyclophosphamide on 1 day). Patients on both arms received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. Additionally, patients were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo. The primary objective was to compare the proportion of patients with no nausea for 5 days following chemotherapy between the 2 study arms. This trial was designed to test for the noninferiority of deleting the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%.

Results: A total of 690 patients were entered on this trial, 50% on each arm. The proportion of patients without nausea for the complete 5-day study period was 7.4% lower (upper limit of the one-sided 95% confidence interval was 13.5%) in the arm without an NK-1 receptor antagonist compared with the arm with an NK-1 receptor antagonist.

Conclusion: This trial did not provide sufficient evidence to support that deletion of the NK-1 receptor antagonist was as good as keeping it, as a part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy

Comments:

The purpose of the protocol was to evaluate the value of an NK-1 receptor antagonist in preventing nausea and vomiting resulting from highly emetogenic chemotherapy when using an olanzapine-based antiemetic regimen. The researchers conducted a prospective double-blind, placebo-controlled clinical trial called A221602.

The trial included patients with a malignant disease who were receiving intravenous highly emetogenic chemotherapy, specifically single-day cisplatin at a dose of 70 mg/m2 or doxorubicin plus cyclophosphamide on a single day. All patients received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. The patients were randomized to receive either an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo in addition to the other antiemetic drugs.

The primary objective of the trial was to compare the proportion of patients who experienced no nausea for five days following chemotherapy between the two study arms. The trial aimed to test the noninferiority of removing the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%.

The results of the trial indicated that a total of 690 patients were enrolled, with 50% assigned to each arm. The proportion of patients without nausea for the complete five-day study period was 7.4% lower in the arm without an NK-1 receptor antagonist compared to the arm with an NK-1 receptor antagonist. The upper limit of the one-sided 95% confidence interval for this difference was 13.5%.

Based on these results, the trial did not provide sufficient evidence to support the deletion of the NK-1 receptor antagonist from the 4-drug antiemetic regimen for highly emetogenic chemotherapy. In other words, the study did not show that removing the NK-1 receptor antagonist was as effective as keeping it in terms of preventing nausea and vomiting in patients undergoing highly emetogenic chemotherapy when using an olanzapine-based antiemetic regimen.