In a Japanese phase III trial reported in the Journal of Clinical Oncology, Inui et al found that the addition of olanzapine to triple antiemetic therapy did not improve the prevention of carboplatin-induced vomiting in patients with thoracic cancers who had received no prior chemotherapy; however, a benefit was observed in preventing chemotherapy-induced nausea.
Study Details
In the double-blind multicenter trial, 355 evaluable patients scheduled to receive a first course of a chemotherapy regimen including carboplatin (area under the curve ≥ 5) were randomly assigned between August 2019 and June 2023 to receive olanzapine at 5 mg (n = 175) or placebo (n = 180) once daily on days 1 to 4 in combination with aprepitant (125 mg on day 1 and 80 mg on days 2–3), a 5-HT3 receptor antagonist on day 1 (palonosetron at 0.75 mg or granisetron at 4 mg/kg intravenously or 2 mg orally), plus dexamethasone at 4.95 mg on day 1.
The primary endpoint of the trial was complete response, defined as no vomiting and no rescue therapy in the overall phase of 0 to 120 hours.
Key Findings
In the overall phase, complete response rates were 86.9% (95% confidence interval [CI] = 80.9%–91.5%) in the olanzapine group vs 80.6% (95% CI = 74.0%–86.1%) in the placebo group (difference = 6.3%, 95% CI = –1.3% to 13.9%, P = .116). Complete response rates were 98.9% vs 97.8% (P = .685) in the acute phase (0–24 hours) and 87.4% vs 80.6% (P = .084) in the delayed phase (24–100 hours).
Higher proportions of patients in the olanzapine group vs the placebo group were free of chemotherapy-induced nausea in the overall phase (88.6% vs 75.0%, P < .001) and the delayed phase (89.7% vs 75.6%, P < .001). No difference was observed in the acute phase (98.9% vs 97.8%, P = .685).
Somnolence—all grade 1 or 2—was observed in 24.6% of patients in the olanzapine group vs 22.9% of those in the placebo group. Constipation (44% vs 44%), hiccups (6% vs 11%), and insomnia (15% vs 20%), all grade 1 or 2, were observed with similar frequency in both groups.
The investigators concluded, “The addition of olanzapine was not associated with a significant increase in the overall complete response rate. Regarding the prevention of nausea, adding olanzapine provided better control in patients receiving carboplatin-containing chemotherapy, which needs further exploration.”
Naoki Inui, MD, PhD, of the Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a Grant-in-Aid from the Japan Research Foundation for Clinical Pharmacology. For full disclosures of the study authors, visit ascopubs.org.
