In a phase III Japanese trial reported in The Lancet Oncology, Saito et al examined the efficacy of adding 5 mg of olanzapine to triplet antiemetic therapy in controlling chemotherapy-induced nausea and vomiting in the overall phase when given after receipt of anthracycline-cyclophosphamide chemotherapy in patients with breast cancer.
Study Details
In the multicenter double-blind trial, 500 patients with stage I to III breast cancer who were chemotherapy-naive or had never received moderately to highly emetogenic chemotherapy were randomly assigned to receive olanzapine (n = 251) or placebo (n = 249) plus standard triplet antiemetic therapy (dexamethasone, palonosetron, aprepitant/fosaprepitant). Olanzapine at 5 mg was given at home within 5 hours after anthracycline plus cyclophosphamide administration on day 1 and on the next 3 days after the evening meal. The primary outcome measure was the proportion of patients with a complete response, defined as no vomiting and no rescue medication during the overall phase of 0 to 120 hours after initiation of chemotherapy.
Key Findings
Among 246 evaluable patients in the olanzapine group, 143 (58.1%) had a complete response in the overall phase vs 83 (35.5%) of 234 in the control group (difference = 22.7%, 95% confidence interval = 14.0–31.4%, P < .0001).
For patient-reported outcomes, the most common severe or very severe adverse events were anorexia (13% in the olanzapine group vs 38% in the control group) and constipation (12% vs 16%). Severe or very severe concentration impairment was reported by 10% vs 14% of patients. Olanzapine-related grade 3 or 4 adverse events included somnolence (2%) and concentration impairment (1%).
The investigators concluded: “Post-chemotherapy administration of 5 mg olanzapine in combination with triplet antiemetic therapy before anthracycline plus cyclophosphamide–based chemotherapy significantly improved the complete response rate for chemotherapy-induced nausea and vomiting during the overall phase compared with placebo in female patients with breast cancer receiving outpatient chemotherapy, with an acceptable level of safety. The findings represent a substantial advancement in managing chemotherapy-induced nausea and vomiting and provide assurance that the safe and effective administration of olanzapine can be achieved at a dosage of 5 mg.”
Mitsue Saito, MD, of the Department of Breast Oncology, Faculty of Medicine, Juntendo University, Tokyo, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by The Capture of Outstanding Clinical Research and Evolution (CORE) project at Juntendo University. For full disclosures of all study authors, visit The Lancet Oncology.
