Kim Ji Hyun, Kim Se Ik, Kim Eun Taeg, Ha Hyeong In, Lee Dong-Eun, Lee Yong Jae, Lee Jung-Yun, Kim Sunghoon, Kim Sang Wun, Kim Young Tae, Park Sang-Yoon, Lim Myong Cheol, Nam Eun-Ji
Center for Gynecologic Cancer, National Cancer Center, Goyang 10408, Republic of Korea.
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Cancers (Basel). 2025 Feb 23;17(5):756. doi: 10.3390/cancers17050756.
The location of BRCA mutations within functional domains may affect sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy. This study aimed to evaluate the progression-free survival (PFS) benefit from the PARP inhibitor in relation to the location of mutations in / in newly diagnosed ovarian cancer.
Patients with advanced stage III-IV epithelial ovarian cancer who had deleterious or were analyzed. PFS and clinical and molecular data were compared between patients who received olaparib or niraparib as frontline maintenance therapy and those who did not. Subgroup analyses were conducted based on the location of mutations within the functional domain or the ovarian cancer cluster region (OCCR).
Of the 380 patients, 242 (63.7%) harbored mutation, 137 (36.1%) harbored , and one (0.3%) harbored both and . With a median follow-up of 35.8 months, the DNA binding domain in (HR, 0.34; 95% CI, 0.15-0.79; = 0.01) and (HR, 0.25; 95% CI, 0.08-0.78; = 0.01) demonstrated particularly significant benefit. In patients who harbored mutation in the C-terminal domain (BRCT), no statistically significant PFS benefit from PARP inhibitor was observed (HR, 0.76; 95% CI, 0.39-1.52; = 0.44). PFS benefit from PARP inhibitor maintenance was observed in both OCCR (HR, 0.49; 95% CI, 0.32-0.74; < 0.01) and non-OCCR (HR, 0.51; 95% CI, 0.27-0.63; < 0.01).
Frontline PARP inhibitor maintenance therapy demonstrated a significant PFS benefit in patients with / mutations, with particularly pronounced benefits for those with mutations located in the DBD of and . However, the benefit was less evident for patients with mutations located in the BRCT domain.
BRCA 突变在功能域内的位置可能会影响对聚（ADP - 核糖）聚合酶（PARP）抑制剂和铂类化疗的敏感性。本研究旨在评估 PARP 抑制剂对新诊断卵巢癌中与突变位置相关的无进展生存期（PFS）的获益情况。
对患有晚期 III - IV 期上皮性卵巢癌且携带有害 或 突变的患者进行分析。比较接受奥拉帕利或尼拉帕利作为一线维持治疗的患者与未接受该治疗的患者的 PFS、临床和分子数据。基于功能域内或卵巢癌簇区域（OCCR）的 突变位置进行亚组分析。
在 380 例患者中，242 例（63.7%）携带 突变，137 例（36.1%）携带 突变，1 例（0.3%）同时携带 和 突变。中位随访 35.8 个月， 在 （HR，0.34；95%CI，0.15 - 0.79； = 0.01）和 （HR，0.25；95%CI，0.08 - 0.78； = 0.01）中的 DNA 结合域显示出特别显著的获益。在 C 末端结构域（BRCT）携带 突变的患者中，未观察到 PARP 抑制剂有统计学意义的 PFS 获益（HR，0.76；95%CI，0.39 - 1.52； = 0.44）。在 OCCR（HR，0.49；95%CI，0.32 - 0.74； < 0.01）和非 OCCR（HR，0.51；95%CI，0.27 - 0.63； < 0.01）中均观察到 PARP 抑制剂维持治疗的 PFS 获益。
一线 PARP 抑制剂维持治疗在携带 / 突变的患者中显示出显著的 PFS 获益，对于那些 在 DBD 中携带突变的患者获益尤为明显。然而，对于在 BRCT 结构域携带 突变的患者，获益不太明显。
