Olanzapine Versus NK1 Receptor Antagonist for Prevention of Carboplatin-Induced (AUC ≥4) Emesis: A Phase III, Double-Blind, Placebo-Controlled Randomized Trial From India

Abstract

PURPOSEPrevention of chemotherapy-induced nausea and vomiting with currently recommended NK1 receptor antagonist–based triplet during carboplatin (AUC ≥4) chemotherapy appears inadequate. A comparative study between olanzapine and NK1 receptor antagonist–based combination is lacking.METHODSThis was a single-center, phase III, prospective randomized, double-blind, placebo-controlled superiority study comparing olanzapine (olanzapine, ondansetron, dexamethasone [OOD]-experimental arm) with fosaprepitant (fosaprepitant, ondansetron, dexamethasone [FOD]-standard arm) in combination with ondansetron and dexamethasone among chemotherapy-naïve patients (age ≥18 years) receiving carboplatin (AUC ≥4) during the first cycle of single-day chemotherapy. The OOD arm received olanzapine 5 mg per oral once daily (day 1-4), ondansetron 8 mg with dexametahsone 12 mg intravenous (IV) once daily (20 mg with paclitaxel; day 1), and matching placebo for fosaprepitant (day 1). The FOD arm received fosaprepitant 150 mg IV once daily, with the combination (day 1) and matching placebo for olanzapine (days 1-4). The primary outcome was no nausea during the overall period (0-120 hours).RESULTSBetween April 2021 and August 2022, a total of 195 patients were evaluable. The proportion of patients without nausea (0 as per Edmonton Symptom Assessment System scale) in OOD versus FOD arms was 44.1% versus 34.4% (P = .19) in the overall period (0-120 hours). Complete response rates and total control rates were also similar in both arms. One patient had grade 3 sedation in the olanzapine arm.CONCLUSIONOlanzapine, in comparison with NK1 antagonist, is not superior for nausea control during carboplatin-induced emesis. It may act as an effective oral alternative for prevention.