Addition of olanzapine to standard chemotherapy-induced nausea and vomiting prophylaxis in hematopoietic stem cell transplant

Abstract

Abstract Purpose: Chemotherapy-induced nausea and vomiting (CINV) remains a significant barrier to quality of life. Hematopoietic cell transplant (HCT) recipients often receive highly emetogenic chemotherapy (HEC) that increases incidence of CINV. Guideline recommendations include olanzapine plus a corticosteroid, serotonin antagonist, and neurokinin-1 antagonist for CINV prophylaxis in patients receiving HEC. However, olanzapine’s role in CINV prevention during HCT has not been evaluated prospectively. Methods: This was a randomized phase 3 trial where olanzapine 5 mg daily was compared to placebo plus a 3-drug CINV regimen during chemotherapy plus three additional days. The primary endpoint was a complete response (CR) defined as no emesis and minimal nausea. Results: Ninety-one HCT recipients (autologous, n=69; allogeneic, n=22) were assessed. The primary endpoint was achieved in 46.7% from the olanzapine arm versus 28.3% from placebo (p=0.085). Median antiemetic doses for breakthrough CINV was significantly less (2 [IQR 0-4]; p=0.003) in the olanzapine arm. Minimal nausea was achieved in 55.6% versus 32.6% of patients, respectively (p=0.04) and fewer rescue antiemetics were required. Adverse events were similar between arms. Conclusion: Addition of olanzapine demonstrated clinical improvements of CR rates among HCT recipients and significant improvements in secondary outcomes. Olanzapine 5 mg daily was safe and tolerable with minimal adverse events.