Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Nanjing, 210009, China.
Department of General Practice, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, 210009, China.
Target Oncol. 2023 Nov;18(6):869-883. doi: 10.1007/s11523-023-00999-x. Epub 2023 Oct 17.
Poly (ADP-ribose) polymerase (PARP) inhibitors are a new maintenance therapy option for patients with ovarian cancer (OC).
To evaluate the efficacy and influencing factors of the novel PARP inhibitor niraparib for maintenance treatment of Chinese patients with advanced OC.
In this retrospective multicenter real-world study patients with advanced OC from 15 hospitals throughout China were enrolled. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included the time to treatment discontinuation and safety. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify possible risk factors for PFS, after which a prediction model was established to evaluate the likelihood of achieving an 18-month PFS. The relationship between the dose of niraparib and PFS was also evaluated.
The PFS rates of 199 patients at 6, 12, 18, 24, and 30 months were 87.4%, 75.9%, 63.6%, 56.1%, and 51.8%, respectively. LASSO regression model revealed that only age < 65 years (P = 0.011), BRCA mutations (P < 0.001), and R0 status after cytoreductive surgery (P = 0.01) were significant factors associated with prolonged PFS times. Based on the LASSO logistic regression analysis, a clinical prediction formula was developed: - 2.412 + 1.396Age + 2.374BRCA + 1.387R + 0.793Interval + 0.178BMI which yielded a cut-off value of 0.091, an area under the curve (AUC) of 0.839 (0.763-0.916), a sensitivity of 94.3%, and an accuracy of 78.5%. A nomogram was then built to visualize the results. The major treatment-emergent adverse events of ≥ grade 3 included a platelet count decrease (19.1%), white blood cell count decrease (15.1%), neutrophil count decrease (13.1%), and anemia (18.6%). The 18-month PFS rates in patients treated with 200 mg niraparib were somewhat higher than in patients treated with 100 mg after 3-months of therapy.
For Chinese OC patients, niraparib, particularly at a 200 mg individual starting dose, was an effective therapy with easily manageable safety.
聚（ADP-核糖）聚合酶（PARP）抑制剂是卵巢癌（OC）患者的一种新的维持治疗选择。
评估新型 PARP 抑制剂尼拉帕利用于中国晚期 OC 患者维持治疗的疗效和影响因素。
本回顾性多中心真实世界研究纳入了来自中国 15 家医院的晚期 OC 患者。主要终点是无进展生存期（PFS），次要终点包括治疗停药时间和安全性。最小绝对收缩和选择算子（LASSO）回归用于确定 PFS 的可能风险因素，然后建立预测模型以评估实现 18 个月 PFS 的可能性。还评估了尼拉帕利剂量与 PFS 的关系。
199 例患者的 6、12、18、24 和 30 个月 PFS 率分别为 87.4%、75.9%、63.6%、56.1%和 51.8%。LASSO 回归模型显示，仅年龄<65 岁（P=0.011）、BRCA 突变（P<0.001）和细胞减灭术后 R0 状态（P=0.01）是与延长 PFS 时间相关的显著因素。基于 LASSO 逻辑回归分析，建立了一个临床预测公式：-2.412+1.396Age+2.374BRCA+1.387R+0.793Interval+0.178BMI，其截断值为 0.091，曲线下面积（AUC）为 0.839（0.763-0.916），灵敏度为 94.3%，准确性为 78.5%。然后构建了一个列线图来可视化结果。≥3 级主要治疗相关不良事件包括血小板计数下降（19.1%）、白细胞计数下降（15.1%）、中性粒细胞计数下降（13.1%）和贫血（18.6%）。接受尼拉帕利 200mg 治疗的患者 18 个月 PFS 率略高于接受尼拉帕利 100mg 治疗 3 个月后的患者。
对于中国 OC 患者，尼拉帕利，特别是以 200mg 的起始剂量，是一种有效的治疗方法，具有易于管理的安全性。
