In an Indian single-center phase III trial reported in The Lancet Oncology, Bajpai et al found that low-dose olanzapine was noninferior to standard-dose olanzapine plus triple antiemetic therapy in terms of antiemetic efficacy and reduced daytime somnolence in patients with solid tumors receiving highly emetogenic chemotherapy.
Study Details
The open-label trial included 267 patients in the modified intent-to-treat (ITT) population receiving doxorubicin/cyclophosphamide or high-dose cisplatin at Tata Memorial Centre. They were randomly assigned between February 2021 and May 2023 to receive either olanzapine at 2.5 mg/d (n = 132) or 10.0 mg/d (n = 135) on days 1 to 4 before sleep, plus triple antiemetic therapy with a 5-HT3 receptor agonist, an NK-1 receptor agonist, and dexamethasone. In total, 91% of patients had breast cancer.
The primary endpoint of the trial was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea in the overall phase (0–120 hours) in the modified ITT population (all eligible patients who received protocol-specified treatment). Daytime somnolence was the primary secondary endpoint.
Our findings suggest that olanzapine [at] 2.5 mg is noninferior to 10.0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care.— Bajpai et al
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Key Findings
In total, 59 patients in the 2.5-mg group (45%) vs 59 in the 10.0-mg group (44%) exhibited complete control during the overall phase (difference = –1.0%, one-sided 95% confidence interval [CI] = –100.0% to 9.0%, P = .87, meeting the noninferiority threshold of 10% for the upper bound of CI).
In the acute phase (0–24 hours), complete control was exhibited by 50% of patients in the 2.5-mg group vs 49% of those in the 10.0-mg group (difference = 1.1%, 95% CI = –13.1% to 10.9%, P = .86). In the overall phase, daytime somnolence of any grade was experienced by 65% of patients in the 2.5-mg group vs 90% of those in the 10.0-mg group (P < .0001); severe-grade somnolence was experienced by 5% vs 40% (P < .0001).
The investigators concluded: “Our findings suggest that olanzapine [at] 2.5 mg is noninferior to 10.0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care.”
Jyoti Bajpai, DM, of the Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the Progressive Ladies Welfare Association. For full disclosures of the study authors, visit thelancet.com.
