Introduction:
Olanzapine 10 mg added to standard antiemetic therapy including aprepitant, palonosetron, and dexamethasone has been recommended for preventing chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy. Guidelines suggest that a dose of 5 mg should be taken into consideration because of sedation. Olanzapine 5 mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate olanzapine 5 mg combined with standard antiemetic therapy for preventing CINV caused by cisplatin-based chemotherapy.

Methods:
Patients receiving cisplatin (≥ 50 mg/m2) were randomly assigned to either olanzapine 5 mg or placebo on days 1–4, combined with aprepitant, palonosetron, and dexamethasone. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120 h). A total of 690 patients were required to detect a 10% increase in CR from 65% in the placebo to 75% in the olanzapine, with a one-sided alpha of 2.5% and a power of 80%.

Results:
A total of 710 patients were enrolled (olanzapine 356, placebo 354). CR in the delayed phase was 79.1% (95% CI: 74.9–83.3) in the olanzapine 5 mg and 65.8% (95% CI: 60.9–70.8) in the placebo (p < 0.001). Other efficacy results are summarized in Table 1. The most common treatment-related adverse event was somnolence (43.1% for olanzapine, 33.0% for placebo).

Conclusions:
Olanzapine 5 mg combined with aprepitant, palonosetron, and dexamethasone can be a new standard antiemetic therapy for cisplatin-based chemotherapy.

12 - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE III TRIAL EVALUATING OLANZAPINE 5 MG AND STANDARD ANTIEMETIC THERAPY FOR PREVENTING CINV CAUSED BY CISPLATIN-BASED CHEMOTHERAPY : J-FORCE STUDY