BRCA mutation status and olaparib-related toxicity during maintenance therapy: a real-world retrospective cohort study.

Objective: Olaparib is a standard maintenance therapy for epithelial ovarian cancer, particularly in patients with BRCA mutations. While BRCA status is an established predictive biomarker for efficacy, its potential impact on treatment-related toxicity remains uncertain. We evaluated the association between BRCA mutation status and the incidence and severity of olaparib-related adverse events in a real-world cohort. Method: This retrospective observational study included patients with epithelial ovarian cancer who received olaparib maintenance therapy at Shandong Provincial Hospital between August 2018 and October 2021. Patients were stratified by BRCA mutation status. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and analyzed at the patient level. Clinically relevant adverse events were defined as grade ≥2, as these typically require medical intervention, closer monitoring, or dose modification. Multivariable logistic regression was performed to adjust for potential confounders. Results: A total of 40 patients were included (24 BRCA-mutant and 16 BRCA wild-type). Clinically relevant adverse events (grade ≥2) occurred more frequently in the BRCA-mutant group than in the BRCA wild-type group (62.5% vs. 18.8%; OR 7.22, 95% CI 1.65-27.42; p = 0.0097). In multivariable analysis adjusting for age and prior chemotherapy cycles, BRCA mutation status remained significantly associated with grade ≥2 adverse events (OR 8.66, 95% CI 1.67-44.81; p = 0.010). Treatment discontinuation due to adverse events was uncommon in both groups. Conclusions: In this real-world retrospective cohort, BRCA mutation status was associated with increased risk of clinically significant olaparib-related toxicity. These findings suggest that BRCA mutation status may help identify patients at higher risk of adverse events and support closer toxicity monitoring and individualized dose management during maintenance therapy.