Impacts of BRCA mutations and clinical factors on niraparib efficacy in patients with platinum-sensitive recurrent ovarian cancer: a retrospective study

BRCA突变和临床因素对铂敏感复发性卵巢癌患者尼拉帕尼疗效的影响:一项回顾性研究

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Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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(2), 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, P = 0.049), BMI ≥ 24 kg/m(2) (HR = 2.317, P = 0.015), CA125 level ≤ 500 U/mL (HR = 2.517, P = 0.005), FIGO stage III/IV (HR = 0.159, P < 0.001; HR = 2.558, P = 0.011), and platinum sensitivity (HR = 2.599, P = 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. CONCLUSION: 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.

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