Table 2_BRCA mutation status and olaparib-related toxicity during maintenance therapy: a real-world retrospective cohort study.docx

ObjectiveOlaparib 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.
MethodThis 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.
ResultsA 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.
ConclusionsIn 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.

研究背景：奥拉帕利（Olaparib）是上皮性卵巢癌的标准维持治疗方案，尤其适用于携带BRCA突变的患者。尽管BRCA状态已被确立为疗效预测的生物标志物，但其对治疗相关毒性的潜在影响仍不明确。本研究在真实世界队列中评估了BRCA突变状态与奥拉帕利相关不良事件的发生率及严重程度之间的关联。

研究方法：本项回顾性观察研究纳入了2018年8月至2021年10月间，在山东省立医院接受奥拉帕利维持治疗的上皮性卵巢癌患者。研究按照BRCA突变状态对患者进行分层。不良事件依据《不良事件通用术语标准5.0版》（Common Terminology Criteria for Adverse Events version 5.0，CTCAE 5.0）进行分级，并以患者为单位开展分析。具有临床意义的不良事件定义为≥2级事件，此类事件通常需要医学干预、强化监测或调整给药剂量。本研究采用多变量logistic回归分析以校正潜在混杂因素。

研究结果：本研究共纳入40例患者（24例BRCA突变型，16例BRCA野生型）。BRCA突变型组中具有临床意义的不良事件（≥2级）发生率显著高于BRCA野生型组（62.5% vs. 18.8%；比值比OR=7.22，95%置信区间CI：1.65~27.42；p=0.0097）。在校正年龄与既往化疗周期数的多变量分析中，BRCA突变状态仍与≥2级不良事件存在显著关联（OR=8.66，95%CI：1.67~44.81；p=0.010）。两组中因不良事件导致治疗中断的情况均较为少见。

研究结论：在本项真实世界回顾性队列研究中，BRCA突变状态与奥拉帕利相关临床显著毒性风险升高相关。上述结果提示，BRCA突变状态可用于识别不良事件风险更高的患者，有助于在维持治疗期间加强毒性监测并实施个体化给药剂量管理。