Olanzapine for chemotherapy-induced nausea and vomiting in breast cancer: a systematic review and meta-analysis of prospective randomised controlled trials

Abstract

Purpose: Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem for breast cancer patients receiving highly emetogenic chemotherapy despite routine antiemetic practice. In this systematic review and meta-analysis we aim to examine the efficacy and safety of olanzapine with regular antiemetic treatment for CINV prevention in breast cancer patients.

Methods: Following PRISMA 2020 standards, we searched PubMed, Cochrane Library, Google scholar, and ClinicalTrials.gov. We retrieved RCTs exclusively, comparing olanzapine with placebo or routine care in breast cancer patients undergoing anthracycline-based chemotherapy. The protocol was registered to PROSPERO (CRD420251087309). The primary outcomes assessed were complete response (defined as no emesis and no rescue medication use) and total control (defined as no nausea, no emesis, and no rescue medication use). Certainty of evidence was assessed using the GRADE approach.

Results: Four RCTs involving 857 patients were included. Compared with placebo or standard antiemetic therapy alone, olanzapine significantly improved complete response rates (4 studies, 857 patients; RR 1.58, 95% CI 1.35-1.85; I² = 0%) and total control (2 studies, 600 patients; RR 1.93, 95% CI 1.49-2.50; I² = 0%). Subgroup analysis showed no statistically significant difference between 5 mg and 10 mg doses. Olanzapine decreased acute nausea (3 studies, 377 patients; RR 1.32, 95% CI 1.03-1.69, I² = 63.4%) and delayed nausea (3 studies, 377 patients; RR 1.22, 95% CI 1.06-1.41, I² = 0%). The overall impact on nausea control was not statistically significant and showed considerable heterogeneity (3 studies, 377 patients; RR 1.42, 95% CI 0.48-4.15; I² = 88.0%). Subgroup analysis showed no statistically significant difference between 5 mg and 10 mg doses. Side effects, including sedation, fatigue, sleeplessness, extrapyramidal symptoms, and increased appetite were significantly attributable to olanzapine. GRADE assessment showed low certainty evidence for complete response, total control, and delayed nausea outcomes, while evidence for acute complete response, acute nausea control, and overall nausea control was rated very low certainty due to risk of bias, inconsistency, and imprecision.

Conclusion: Olanzapine significantly enhances CINV prevention in breast cancer patients, with positive outcomes for both 5 mg and 10 mg doses. Although increased sedation occurred, it was generally well-tolerated.

Keywords: Antiemetic; Breast cancer; Chemotherapy-induced nausea and vomiting (CINV); Olanzapine.