Kim Nam Kyeong, Kim Yeorae, Kim Hee Seung, Park Soo Jin, Hwang Dong Won, Lee Sung Jong, Yoo Ji Geun, Chang Suk-Joon, Son Joo-Hyuk, Kong Tae-Wook, Kim Jeeyeon, Shim Seung-Hyuk, Lee A Jin, Suh Dong Hoon, Lee Yoo-Young
Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
Cancer Med. 2023 Oct;12(19):19449-19459. doi: 10.1002/cam4.6546. Epub 2023 Sep 28.
To identify the risk factors for failure of first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy in patients with advanced ovarian cancer.
Patients with stage III-IV epithelial ovarian cancer who received first-line PARPi maintenance therapy were retrospectively reviewed. Clinicopathologic factors were compared between two groups-recur/progression of disease (PD) and non-recur/PD.
In total, 191 patients were included. Median follow-up was 9.9 months, and recurrence rate was 20.9%. BRCA mutations were found in 63.4% patients. Postoperative residual tumor (60.5% vs. 37.8%), non-high grade serous carcinoma (HGSC) (15.0% vs. 6.0%), neoadjuvant chemotherapy (NAC) (55.0% vs. 35.8%), and pre-PARPi serum CA-125 levels ≥23.5 U/mL (35.9% vs. 15.2%) were more frequently observed in the recur/PD group. Multivariate Cox-regression analysis revealed pre-PARPi serum CA-125 levels ≥23.5 U/mL (HR, 2.17; 95%CI, 1.03-4.57; p = 0.042), non-HGSC (3.28; 1.20-8.97; p = 0.021), NAC (2.11; 1.04-4.26; p = 0.037), and no BRCA mutation (2.23; 1.12-4.44; p = 0.023) as independent risk factors associated with poor progression-free survival (PFS). A subgroup analysis according to BRCA mutation status showed that pre-PARPi serum CA-125 levels ≥26.4 U/mL were the only independent risk factor for poor PFS in women with BRCA mutations (2.75; 1.03-7.39; p = 0.044). Non-HGSC (5.05; 1.80-14.18; p = 0.002) and NAC (3.36; 1.25-9.04; p = 0.016) were independent risk factors in women without BRCA mutations.
High pre-PARPi serum CA-125 levels, non-HGSC histology, NAC, and no BRCA mutation might be risk factors for early failure of first-line PARPi maintenance therapy. In women with BRCA mutations, high pre-PARPi serum CA-125 levels, which represent a large tumor burden before PARPi, were the only independent risk factor for poor PFS.
确定晚期卵巢癌患者一线聚（ADP - 核糖）聚合酶抑制剂（PARPi）维持治疗失败的风险因素。
回顾性分析接受一线PARPi维持治疗的Ⅲ - Ⅳ期上皮性卵巢癌患者。比较疾病复发/进展（PD）组和非复发/PD组的临床病理因素。
共纳入191例患者。中位随访时间为9.9个月，复发率为20.9%。63.4%的患者检测到BRCA突变。复发/PD组更常观察到术后残留肿瘤（60.5%对37.8%）、非高级别浆液性癌（HGSC）（15.0%对6.0%）、新辅助化疗（NAC）（55.0%对35.8%）以及PARPi治疗前血清CA - 125水平≥23.5 U/mL（35.9%对15.2%）。多因素Cox回归分析显示，PARPi治疗前血清CA - 125水平≥23.5 U/mL（HR，2.17；95%CI，1.03 - 4.57；p = 0.042）、非HGSC（3.28；1.20 - 8.97；p = 0.021）NAC（2.11；1.04 - 4.26；p = 0.037）以及无BRCA突变（2.23；1.12 - 4.44；p = 0.023）是与无进展生存期（PFS）不佳相关的独立风险因素。根据BRCA突变状态进行的亚组分析表明，PARPi治疗前血清CA - 125水平≥26.4 U/mL是BRCA突变女性PFS不佳的唯一独立风险因素（2.75；1.03 - 7.39；p = 0.044）。非HGSC（5.05；1.80 - 14.18；p = 0.002）和NAC（3.36；1.25 - 9.04；p = 0.016）是无BRCA突变女性的独立风险因素。
PARPi治疗前血清CA - 125水平高、非HGSC组织学类型、NAC以及无BRCA突变可能是一线PARPi维持治疗早期失败的风险因素。在BRCA突变的女性中，PARPi治疗前血清CA - 125水平高代表PARPi治疗前肿瘤负荷大，是PFS不佳的唯一独立风险因素。
