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)

Authors

Rudolph M. Navari, Department of Hematology Oncology, Simon Williamson Clinic, Birmingham, AL, USA.
Jennifer Le-Rademacher, Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA.
Fabrice Smieliauskas, Department of Hematology Oncology, Wayne State University, Detroit, MI, USA.
Kathryn J. Ruddy, Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
Thomas James Saphner, Advocate Aurora HealthFollow
Heshan Liu, Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA.
Elizabeth Harlos, Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA.
Adedayo A. Onitilo, Department of Hematology Oncology, Marshfield Clinic-Weston Center, Marshfield, WI, USA.
Karthik Giridhar, Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
Preet Paul Singh, Department of Hematology Oncology, Springfield Clinic, Heartland NCORP, Springfield, IL, USA.
Pavan S. Reddy, Department of Hematology Oncology, Cancer Center of Kansas, Wichita, KS, USA.
Selina Chow, Alliance Protocol Operations Office, University of Chicago, Chicago, IL, USA.
Flavio Kruter, Department of Hematology Oncology, Carroll Regional Cancer Center, Westminster, MD, USA.
George Raptis, Department of Hematology Oncology, Northwell Health Cancer Institute, Lake Success, NY, USA.
Charles L. Loprinzi, Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA.

Recommended Citation

Navari RM, Le-Rademacher J, Smieliauskas F, et al. 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). Oncologist. 2023;28(8):722-729. doi:10.1093/oncolo/oyad140

Affiliations

Green Bay, WI

Abstract

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 (ClinicalTrials.gov Identifier: NCT03578081 ).

Document Type

Article

PubMed ID

37284847