Ni Jing, Guo Wenwen, Zhao Qian, Cheng Xianzhong, Xu Xia, Zhou Rui, Gu Hongyuan, Chen Chen, Chen Xiaoxiang
Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Oncol. 2022 Jan 6;11:746571. doi: 10.3389/fonc.2021.746571. eCollection 2021.
Homologous recombination deficiency (HRD) is an approved predictive biomarker for Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. However, the proportion of positive HRD in the real world and the relationship between HRD status and PARPi in Chinese ovarian cancer patients remain unknown. A total of 67 ovarian cancer patients who underwent PARPi, either olaparib or niraparib, were enrolled and passed inclusion criteria from August 2018 to January 2021 in the Affiliated Cancer Hospital of Nanjing Medical University. HRD status correlation with Progression-free survival (PFS) was analyzed and summarized with a log-rank test. Univariate and multiple cox-regression analyses were conducted to investigate all correlated clinical factors. Approximately 68.7% (46/67) patients were HRD positive and the rest 31.3% (21/67) were HRD negative. The PFS among HRD-positive patients was significantly longer than those HRD-negative patients (medium PFS 9.4 m vs 4.1 m, hazard ratio [HR]: 0.52, 95% CI: [0.38-0.71], p <0.001). Univariate cox-regression found that HRD status, Eastern Cooperative Oncology Group (ECOG) status, BRCA status, previous treatment lines, secondary cytoreductive surgery and R0 resection were significantly associated with PFS after PARPi treatment. After multiple regression correction, HRD status and ECOG were the independent factors to predict PFS (HR: 0.67, 95% CI: [0.49-0.92], p = 0.01; HR: 2.20, 95% CI: [1.14-4.23], p = 0.02, respectively). In platinum sensitivity evaluable subgroup (N = 49), HRD status and platinum sensitivity status remain significant to predict PFS after multiple regression correction (HR: 0.71, 95% CI: [0.51-0.98], p = 0.04; HR: 0.49, 95% CI: [0.24-1.0], p = 0.05, respectively). This is the first real-world study of HRD status in ovarian cancer patients in China, and we demonstrate that HRD is an independent predictive biomarker for PARP inhibitors treatment in Chinese ovarian cancer patients.
同源重组缺陷(HRD)是卵巢癌中聚(ADP - 核糖)聚合酶抑制剂(PARPi)的一种已获批准的预测生物标志物。然而,中国卵巢癌患者中HRD阳性的比例以及HRD状态与PARPi之间的关系仍不清楚。2018年8月至2021年1月,南京医科大学附属肿瘤医院共纳入67例接受PARPi(奥拉帕利或尼拉帕利)治疗且符合纳入标准的卵巢癌患者。采用对数秩检验分析并总结HRD状态与无进展生存期(PFS)的相关性。进行单因素和多因素cox回归分析以研究所有相关临床因素。约68.7%(46/67)的患者HRD阳性,其余31.3%(21/67)为HRD阴性。HRD阳性患者的PFS显著长于HRD阴性患者(中位PFS 9.4个月对4.1个月,风险比[HR]:0.52,95%置信区间[CI]:[0.38 - 0.71],p <0.001)。单因素cox回归发现,HRD状态、东部肿瘤协作组(ECOG)状态、BRCA状态、既往治疗线数、二次减瘤手术和R0切除与PARPi治疗后的PFS显著相关。多因素回归校正后,HRD状态和ECOG是预测PFS的独立因素(HR分别为:0.67,95% CI:[0.49 - 0.92],p = 0.01;HR:2.20,95% CI:[1.14 - 4.23],p = 0.02)。在铂敏感性可评估亚组(N = 49)中,多因素回归校正后,HRD状态和铂敏感性状态对预测PFS仍具有显著意义(HR分别为:0.71,95% CI:[0.51 - 0.98],p = 0.04;HR:0.49,95% CI:[0.24 - 1.0],p = 0.05)。这是中国首次对卵巢癌患者HRD状态进行的真实世界研究,我们证明HRD是中国卵巢癌患者PARP抑制剂治疗的独立预测生物标志物。