Hu Zheyu, Li Li, Yang Zhe, Liu Yingchun, Dong Lijun, Li Fang
Department of Obstetrics and Gynaecology, Affiliated Nanhua Hospital, University of South China Hengyang 421000, Hunan, China.
Department of Gynecology, Hengyang Maternal and Child Health Hospital Hengyang 421000, Hunan, China.
Am J Cancer Res. 2025 May 15;15(5):2056-2076. doi: 10.62347/FGLY8019. eCollection 2025.
To investigate the impacts of breast cancer gene (BRCA) mutations, clinical factors such as body mass index (BMI), carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), International Federation of Gynecology and Obstetrics (FIGO) staging and platinum sensitivity, and pathological characteristics on progression-free survival (PFS) in platinum-sensitive recurrent ovarian cancer (PSROC) patients treated with niraparib, and to identify independent prognostic factors for treatment outcomes.
A total of 312 patients with ovarian cancer undergoing treatment between Jan. 2020 and Jan. 2022 were selected for the retrospective study. Patients were eligible if they were ≥ 18 years old and diagnosed with epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. In addition, they received platinum-sensitive treatment (PFS ≥ 6 months) and niraparib as a maintenance therapy. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the influence of clinical and pathological variables on PFS. Time-dependent receiver operating characteristic (ROC) curve analysis was performed to assess the predictive power of significant factors.
Univariate Cox regression analysis identified significant associations between patients' PFS and BRCA mutation status, BMI, CA125 levels, FIGO staging, platinum sensitivity, and niraparib usage and timing. Patients with BRCA mutations, BMI ≥ 24 kg/m, CA125 level ≤ 500 U/mL, FIGO stage II, or platinum sensitivity demonstrated a significantly longer PFS. Multivariate Cox regression analysis confirmed BRCA mutations (hazard ratio (HR) = 1.754, = 0.049), BMI ≥ 24 kg/m (HR = 2.317, = 0.015), CA125 level ≤ 500 U/mL (HR = 2.517, = 0.005), FIGO stage III/IV (HR = 0.159, < 0.001; HR = 2.558, = 0.011), and platinum sensitivity (HR = 2.599, = 0.043) as independent predictors for PFS. Time-dependent ROC analysis demonstrated that platinum sensitivity and FIGO staging were the most influential prognostic factors to predict the 1-year and 3-year PFS. In addition, it was found that niraparib-associated adverse events occurred in 62.84% of the enrolled patients, primary of which were mild to moderate hematological and gastrointestinal toxicities.
BRCA mutations, CA125 levels, FIGO staging, BMI, and platinum sensitivity are critical factors influencing the efficacy of niraparib in PSROC patients. These findings have provided valuable insights into the individualized application of niraparib and the optimization of treatment strategies for PSROC patients.
探讨乳腺癌基因（BRCA）突变、体重指数（BMI）、糖类抗原125（CA125）、人附睾蛋白4（HE4）、国际妇产科联盟（FIGO）分期、铂敏感性等临床因素以及病理特征对接受尼拉帕利治疗的铂敏感复发性卵巢癌（PSROC）患者无进展生存期（PFS）的影响，并确定治疗结局的独立预后因素。
选取2020年1月至2022年1月期间接受治疗的312例卵巢癌患者进行回顾性研究。患者年龄≥18岁，诊断为上皮性卵巢癌、输卵管癌或原发性腹膜癌，且接受过铂敏感治疗（PFS≥6个月）并接受尼拉帕利维持治疗者符合入选标准。采用单因素和多因素Cox比例风险回归模型评估临床和病理变量对PFS的影响。进行时间依赖性受试者工作特征（ROC）曲线分析以评估显著因素的预测能力。
单因素Cox回归分析确定患者的PFS与BRCA突变状态、BMI、CA125水平、FIGO分期、铂敏感性、尼拉帕利的使用及用药时机之间存在显著关联。BRCA突变、BMI≥24 kg/m、CA125水平≤500 U/mL、FIGO II期或铂敏感的患者PFS显著更长。多因素Cox回归分析证实BRCA突变（风险比（HR）=1.754，P=0.049）、BMI≥24 kg/m（HR = 2.317，P = 0.015）、CA125水平≤500 U/mL（HR = 2.517，P = 0.005）、FIGO III/IV期（HR = 0.159，P<0.001；HR = 2.558，P = 0.011）和铂敏感性（HR = 2.599，P = 0.043）是PFS的独立预测因素。时间依赖性ROC分析表明，铂敏感性和FIGO分期是预测1年和3年PFS最具影响力的预后因素。此外，发现62.84%的入组患者发生了与尼拉帕利相关的不良事件，主要为轻度至中度血液学和胃肠道毒性。
BRCA突变、CA125水平、FIGO分期、BMI和铂敏感性是影响尼拉帕利治疗PSROC患者疗效的关键因素。这些发现为尼拉帕利的个体化应用及PSROC患者治疗策略的优化提供了有价值的见解。
