Olanzapine combined with standard antiemetics for the prevention of nausea and vomiting in patients with germ cell tumor undergoing a 5-day cisplatin-based chemotherapy (NAVIGATE study)： A phase III crossover trial.

Purpose Prophylactic use of olanzapine significantly improves chemotherapy-induced nausea and vomiting (CINV) in patients receiving single-day highly emetogenic chemotherapy and 3-day cisplatin-based chemotherapy. This phase III, double-blind, placebo-controlled crossover trial aimed to evaluate the efficacy and safety of olanzapine combined with triple antiemetic therapy for CINV in germ cell tumor (GCT) patients receiving 5-day cisplatin-based chemotherapy.Methods Eligible patients receiving at least two consecutive identical courses of 5-day cisplatin-based chemotherapy were randomly assigned to either olanzapine (5 mg) or its matching placebo during days 1-7 of the first chemotherapy cycle, then crossed over to the alternate group during the second cycle. The primary endpoint was complete response (CR) rate. Main secondary endpoints included CR rates in acute and delayed phases, no nausea rates, and toxicities. Results Between January 2022 and February 2024, 77 patients were enrolled, 40 were randomized to the olanzapine group, and 37 to the placebo group during the first course. The overall CR rate was 55.8 % (43/77) in the olanzapine group, compared with 36.3 % (28/77) in the placebo group (P = 0.03). The CR rates in the acute and delayed phases were 62.3 % (48/77) vs. 40.3 % (31/77), P = 0.01, and 79.2 % (61/77) vs. 53.2 % (41/77), P = 0.04, respectively. No nausea rates were also significantly higher in the olanzapine group than those in the placebo group: 36.4 % vs. 15.6 % in overall phase (P = 0.005), 39.0 % vs.16.9 % in acute phase (P = 0.004) and 72.7 % vs. 49.4 % in delayed phase (P = 0.005). Addition of olanzapine did not increase toxicities. Conclusion This trial provides the first high-level evidence supporting the olanzapine-based four-drug combination to prevent CINV in GCT patients undergoing 5-day cisplatin-based chemotherapy. Clinical Trial Registration: ClinicalTrials.gov, number NCT05198796.