Olanzapine 5mg in Combination with Standard Antiemetic Therapy for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Cisplatin-Based Chemotherapy (J-FORCE): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial

Background: Olanzapine 10 mg added to standard antiemetic therapy, including aprepitant, palonosetron, and dexamethasone, has been recommended for the prevention of chemotherapy-induced nausea and vomiting. Guidelines suggest that a dose reduction to 5 mg may be considered to prevent sedation. In several phase II studies, olanzapine 5 mg has shown equivalent activity and a favourable safety profile in relation to somnolence. We conducted a randomised, double-blinded, placebo-controlled, phase III study (J-FORCE) to evaluate olanzapine 5 mg combined with standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting caused by cisplatin-based chemotherapy. Methods: This was a multicentre, phase III study to evaluate olanzapine 5 mg with triplet-combination therapy. Patients receiving cisplatin ((≥50 mg/m2) were randomly assigned to receive oral olanzapine 5 mg or placebo once daily on days 1-4 combined with aprepitant, palonosetron, and dexamethasone (dosage based on the standard antiemetic therapy against highly emetogenic chemotherapy). The primary endpoint was the proportion of complete response (CR), defined as absence of vomiting and no use of rescue medications in the delayed phase (24-120 hours). Findings: Between February 9, 2017 and July 13, 2018, 710 patients were enrolled from 26 hospitals in Japan. Of those, 356 and 354 patients were randomly assigned to the olanzapine and placebo groups, respectively. In the delayed phase, CR was 79% (95% CI: 75-83) in the olanzapine 5 mg group and 66% (95% CI: 61-71)a€€in the placebo group (p