Current research status on poly ADP-ribose polymerase inhibitors and regulation of immunotherapy for patients with ovarian cancer

doi:10.3877/cma.j.issn.1673-5250.2026.01.003

Ovarian cancer ranks as the gynecological malignancy with the highest mortality rate, with approximately 70% of patients presenting at an advanced stage upon clinical diagnosis. Despite conventional treatment involving surgery plus platinum-based chemotherapy, the recurrence rate remains high. The tumor immune microenvironment of ovarian cancer exhibits typical " cold tumor" features, contributing to a suboptimal objective response rate (ORR) of ≤10% with immune checkpoint inhibitor (ICI) monotherapy. In recent years, studies have demonstrated that poly ADP-ribose polymerase (PARP) inhibitors not only target DNA repair defects in cancer cells via the " synthetic lethality" pathway, but also exert a pivotal role in remodeling the tumor immune microenvironment. Clinical evidence indicates that combination therapy with PARP inhibitors and ICI enhances the ORR in ovarian cancer patients; yet, optimizing this combination regimen remains challenging to date. This review summarizes the latest advances in the ovarian cancer tumor immune microenvironment, the therapeutic efficacy and regulatory effects of PARP inhibitors in ovarian cancer immunotherapy, with the goal of providing insights for developing immunotherapy strategies for ovarian cancer patients in the era of PARP inhibitors maintenance therapy.

Key words: Tumor microenvironment, Immunosuppressive agents, Poly(ADP-ribose) polymerase inhibitors, Immunotherapy, Immune checkpoint inhibitor, Female

表1 ICI单药治疗复发性铂耐药卵巢癌患者的临床研究结果比较

试验名称	免疫药物	患者特征	样本量(例)	主要终点	结果
KEYNOTE-100^[25]	帕博利珠单抗(pembrolizumab)	复发性卵巢癌(铂耐药/铂敏感)	376	ORR	总体ORR为8%，在PD-L1高表达亚组(CPS≥10分)中，则ORR更高
JAVELIN Ovarian 100^[26]	阿维鲁单抗(avelumab)vs化疗(卡铂＋紫杉醇)	初治上皮性卵巢癌	998	PFS期	阿维鲁单抗维持治疗组PFS期为11.6个月，化疗对照组为11.5个月
NINJA^[27]	纳武利尤单抗(nivolumab)vs化疗(吉西他滨/聚乙二醇化脂质体阿霉素)	复发性铂耐药卵巢癌	316	OS期	①OS期：nivolumab组为10.12个月，化疗组为12.09个月(HR＝1.03，P＝0.808)。②PFS期(次要终点)：nivolumab组为2.04个月，化疗组为3.84个月(HR＝1.46，P＝0.002)

表1 ICI单药治疗复发性铂耐药卵巢癌患者的临床研究结果比较

试验名称	免疫药物	患者特征	样本量(例)	主要终点	结果
KEYNOTE-100^[25]	帕博利珠单抗(pembrolizumab)	复发性卵巢癌(铂耐药/铂敏感)	376	ORR	总体ORR为8%，在PD-L1高表达亚组(CPS≥10分)中，则ORR更高
JAVELIN Ovarian 100^[26]	阿维鲁单抗(avelumab)vs化疗(卡铂＋紫杉醇)	初治上皮性卵巢癌	998	PFS期	阿维鲁单抗维持治疗组PFS期为11.6个月，化疗对照组为11.5个月
NINJA^[27]	纳武利尤单抗(nivolumab)vs化疗(吉西他滨/聚乙二醇化脂质体阿霉素)	复发性铂耐药卵巢癌	316	OS期	①OS期：nivolumab组为10.12个月，化疗组为12.09个月(HR＝1.03，P＝0.808)。②PFS期(次要终点)：nivolumab组为2.04个月，化疗组为3.84个月(HR＝1.46，P＝0.002)

表2 PARP抑制剂联合ICI治疗复发性铂耐药卵巢癌患者的临床研究结果比较

试验名称	分组	结果
TOPACIO/KEYNOTE-162^[34]	复发卵巢癌(不限BRCA状态)组(n＝55)，采取尼拉帕利＋帕博利珠单抗治疗	ORR为18%(3例为CR，8例为PR)，DCR为65%
DUO-O^[32]	研究对象均为非BRCA突变HRD呈阳性和非BRCA突变ITT卵巢癌患者。化疗阶段：组1(n＝143)采取卡铂/紫杉醇＋贝伐珠单抗治疗措施；组2(n＝148)采取卡铂/紫杉醇＋贝伐珠单抗＋度伐利尤单抗治疗措施；组3(n＝140)采取卡铂/紫杉醇＋贝伐珠单抗＋度伐利尤单抗治疗措施。维持治疗阶段：组1采取贝伐珠单抗单独治疗＋安慰剂治疗措施；组2采取贝伐珠单抗＋度伐利尤单抗治疗＋安慰剂治疗措施；组3采取贝伐珠单抗＋度伐利尤单抗＋奥拉帕利治疗措施	非BRCA突变HRD呈阳性患者中的mPFS期：组1、2、3分别为23.0、24.4、37.3个月。非BRCA突变ITT患者中的mPFS期：组1、2、3分别为19.3、20.6、24.2个月，组1 vs组3(HR＝0.63，95%CI：0.52~0.76，P<0.000 1)
ENGOT-OV41/GEICO 69-O/ANITA^[33]	研究对象：417例患者，其中15%为BRCA突变者(n＝63)，36%为PD-L1呈阳性者(n＝150)，66%为TFIP>12个月者(n＝275)。联合组(n＝209)：采取阿替利珠单抗＋6个周期卡铂双药化疗，疾病缓解/稳定后序贯尼拉帕利维持治疗措施；标准组(n＝208)：采取安慰剂＋6个周期卡铂双药化疗，疾病缓解/稳定后序贯尼拉帕利维持治疗措施	PFS期：联合组、标准组分别为11.2、10.1个月(HR＝0.89，95%CI：0.71~1.10，P＝0.28)

表2 PARP抑制剂联合ICI治疗复发性铂耐药卵巢癌患者的临床研究结果比较

试验名称	分组	结果
TOPACIO/KEYNOTE-162^[34]	复发卵巢癌(不限BRCA状态)组(n＝55)，采取尼拉帕利＋帕博利珠单抗治疗	ORR为18%(3例为CR，8例为PR)，DCR为65%
DUO-O^[32]	研究对象均为非BRCA突变HRD呈阳性和非BRCA突变ITT卵巢癌患者。化疗阶段：组1(n＝143)采取卡铂/紫杉醇＋贝伐珠单抗治疗措施；组2(n＝148)采取卡铂/紫杉醇＋贝伐珠单抗＋度伐利尤单抗治疗措施；组3(n＝140)采取卡铂/紫杉醇＋贝伐珠单抗＋度伐利尤单抗治疗措施。维持治疗阶段：组1采取贝伐珠单抗单独治疗＋安慰剂治疗措施；组2采取贝伐珠单抗＋度伐利尤单抗治疗＋安慰剂治疗措施；组3采取贝伐珠单抗＋度伐利尤单抗＋奥拉帕利治疗措施	非BRCA突变HRD呈阳性患者中的mPFS期：组1、2、3分别为23.0、24.4、37.3个月。非BRCA突变ITT患者中的mPFS期：组1、2、3分别为19.3、20.6、24.2个月，组1 vs组3(HR＝0.63，95%CI：0.52~0.76，P<0.000 1)
ENGOT-OV41/GEICO 69-O/ANITA^[33]	研究对象：417例患者，其中15%为BRCA突变者(n＝63)，36%为PD-L1呈阳性者(n＝150)，66%为TFIP>12个月者(n＝275)。联合组(n＝209)：采取阿替利珠单抗＋6个周期卡铂双药化疗，疾病缓解/稳定后序贯尼拉帕利维持治疗措施；标准组(n＝208)：采取安慰剂＋6个周期卡铂双药化疗，疾病缓解/稳定后序贯尼拉帕利维持治疗措施	PFS期：联合组、标准组分别为11.2、10.1个月(HR＝0.89，95%CI：0.71~1.10，P＝0.28)

[1]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263. DOI：10.3322/caac.21834.
[2]	Disis ML, Taylor MH, Kelly K, et al. Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: phase 1b results from the JAVELIN solid tumor trial[J]. JAMA Oncol, 2019, 5(3): 393-401. DOI：10.1001/jamaoncol.2018.6258.
[3]	Ding L, Kim HJ, Wang Q, et al. PARP inhibition elicits sting-dependent antitumor immunity in brca1-deficient ovarian cancer[J]. Cell Rep, 2018, 25(11): 2972-2980.e5. DOI：10.1016/j.celrep.2018.11.054.
[4]	Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment[J]. Cancer Cell, 2012, 21(3): 309-322. DOI: 10.1016/j.ccr.2012.02.022.
[5]	Jayson GC, Kerbel R, Ellis LM, et al. Antiangiogenic therapy in oncology: current status and future directions[J]. Lancet, 2016, 388(10043): 518-529. DOI: 10.1016/S0140-6736(15)01088-0.
[6]	Truxova I, Kasikova L, Hensler M, et al. Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients[J]. J Immunother Cancer, 2018, 6(1): 139. DOI: 10.1186/s40425-018-0446-3.
[7]	Sun J, Yan C, Xu D, et al. Immuno-genomic characterisation of high-grade serous ovarian cancer reveals immune evasion mechanisms and identifies an immunological subtype with a favourable prognosis and improved therapeutic efficacy[J]. Br J Cancer, 2022, 126(11): 1570-1580. DOI: 10.1038/s41416-021-01692-4.
[8]	Mateiou C, Lokhande L, Diep LH, et al. Spatial tumor immune microenvironment phenotypes in ovarian cancer[J]. NPJ Precis Oncol, 2024, 8(1): 148. DOI：10.1038/s41698-024-00640-8.
[9]	Odunsi K. Immunotherapy in ovarian cancer[J]. Ann Oncol, 2017, 28(Suppl_8): viii1-viii7. DOI: 10.1093/annonc/mdx444.
[10]	Ghisoni E, Morotti M, Sarivalasis A, et al. Immunotherapy for ovarian cancer: towards a tailored immunophenotype-based approach[J]. Nat Rev Clin Oncol, 2024, 21(11): 801-817. DOI: 10.1038/s41571-024-00937-4.
[11]	Ghisoni E, Benedetti F, Minasyan A, et al. Myeloid cell networks govern re-establishment of original immune landscapes in recurrent ovarian cancer[J].Cancer Cell, 2025, 43(8): 1568.e10-1586.e10. DOI：10.1016/j.ccell.2025.07.005.
[12]	Li YR, Ochoa CJ, Zhu Y, et al. Profiling ovarian cancer tumor and microenvironment during disease progression for cell-based immunotherapy design[J].iScience, 2023, 26(10): 107952. DOI: 10.1016/j.isci.2023.107952.
[13]	卢淮武，霍楚莹，黄纯娴，等. 《2025 NCCN卵巢癌包括输卵管癌及原发性腹膜癌临床实践指南(第1版)》解读[J]. 中国实用妇科与产科杂志，2025, 41(4): 436-444. DOI: 10.19538/j.fk2025040113.
[14]	Scott CL, Swisher EM, Kaufmann SH. Poly (ADP-ribose) polymerase inhibitors: recent advances and future development[J]. J Clin Oncol, 2015, 33(12): 1397-1406. DOI: 10.1200/JCO.2014.58.8848.
[15]	DiSilvestro P, Banerjee S, Colombo N, et al. Overall survival with maintenance olaparib at a 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: the SOLO1/GOG 3004 trial[J]. J Clin Oncol, 2023, 41(3): 609-617. DOI: 10.1200/JCO.22.01549.
[16]	Monk BJ, Barretina-Ginesta MP, Pothuri B, et al. Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial[J]. Ann Oncol, 2024, 35(11): 981-992. DOI: 10.1016/j.annonc.2024.08.2241.
[17]	孔北华，刘继红，崔恒，等. 卵巢癌PARP抑制剂临床应用指南(2025版)[J].现代妇产科进展，2025, 34(2): 81-94. DOI: 10.13283/j.cnki.xdfckjz.2025.02.001.
[18]	Malmberg R, Zietse M, Dumoulin DW, et al. Alternative dosing strategies for immune checkpoint inhibitors to improve cost-effectiveness: a special focus on nivolumab and pembrolizumab[J]. Lancet Oncol, 2022, 23(12): e552-e561. DOI: 10.1016/S1470-2045(22)00554-X.
[19]	Laskowski TJ, Biederstädt A, Rezvani K. Natural killer cells in antitumour adoptive cell immunotherapy[J]. Nat Rev Cancer, 2022, 22(10): 557-575. DOI: 10.1038/s41568-022-00491-0.
[20]	Li Y, Ma X, Yue Y，et al. Rapid surface display of mRNA antigens by bacteria-derived outer membrane vesicles for a personalized tumor vaccine[J]. Adv Mater, 2022, 34(20): e2109984. DOI: 10.1002/adma.202109984.
[21]	Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma[J]. N Engl J Med, 2015, 373(1): 23-34. DOI: 10.1056/NEJMoa1504030.
[22]	Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-positive non-small-cell lung cancer[J]. N Engl J Med, 2016, 375(19): 1823-1833. DOI: 10.1056/NEJMoa1606774.
[23]	Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma[J]. N Engl J Med, 2017, 377(26): 2531-2544. DOI: 10.1056/NEJMoa1707447.
[24]	Konstantinopoulos PA, Cannistra SA. Immune checkpoint inhibitors in ovarian cancer: can we bridge the gap between imagynation and reality[J]. J Clin Oncol, 2021, 39(17): 1833-1838. DOI: 10.1200/JCO.21.00571.
[25]	Matulonis UA, Shapira-Frommer R, Santin AD, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase Ⅱ KEYNOTE-100 study[J]. Ann Oncol, 2019, 30(7): 1080-1087. DOI: 10.1093/annonc/mdz135.
[26]	Monk BJ, Colombo N, Oza AM, et al. Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial[J]. Lancet Oncol, 2021, 22(9): 1275-1289. DOI: 10.1016/S1470-2045(21)00342-9.
[27]	Hamanishi J, Takeshima N, Katsumata N, et al. Nivolumab versus gemcitabine or pegylated liposomal doxorubicin for patients with platinum-resistant ovarian cancer: open-label, randomized trial in Japan (NINJA)[J]. J Clin Oncol, 2021, 39(33): 3671-3681. DOI: 10.1200/JCO.21.00334.
[28]	Musacchio L, Cicala CM, Camarda F, et al. Combining PARP inhibition and immune checkpoint blockade in ovarian cancer patients: a new perspective on the horizon[J]. ESMO Open, 2022, 7(4): 100536. DOI: 10.1016/j.esmoop.2022.100536.
[29]	Harter P, Trillsch F, Okamoto A, et al. Durvalumab with paclitaxel/carboplatin (PC) and bevacizumab (bev), followed by maintenance durvalumab, bev, and olaparib in patients (pts) with newly diagnosed advanced ovarian cancer (AOC) without a tumor BRCA1/2 mutation (non-tBRCAm): results from the randomized, placebo (pbo)-controlled phase Ⅲ DUO-O trial[J]. J Clin Oncol, 2023, 41(17_suppl): LBA5506. DOI：10.1200/JCO.2023.41.17_suppl.LBA5506.
[30]	Westin SN, Moore KN, Chon HS, et al. LBA41 durvalumab (durva) plus carboplatin/paclitaxel (CP) followed by maintenance (mtx) durva ± olaparib (ola) as a first-line (1L) treatment for newly diagnosed advanced or recurrent endometrial cancer (EC): results from the phase Ⅲ DUO-E/GOG-3041/ENGOT-EN10 trial[J]. Ann Oncol, 2023, 34: S1282-S1283. DOI: 10.1016/j.annonc.2023.10.035.
[31]	Domchek SM, Postel-Vinay S, Im SA, et al. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study[J]. Lancet Oncol, 2020, 21(9): 1155-1164. DOI: 10.1016/S1470-2045(20)30324-7.
[32]	Harter P, Trillsch F, Okamoto A, et al. Durvalumab with carboplatin/paclitaxel and bevacizumab followed by durvalumab and bevacizumab with or without olaparib maintenance in newly diagnosed non-BRCA-mutated advanced ovarian cancer[J].Ann Oncol, 2026, 37(4): 503-520. DOI：10.1016/j.annonc.2025.11.020.
[33]	González-Martín A, Rubio MJ, Heitz F, et al. Atezolizumab combined with platinum and maintenance niraparib for recurrent ovarian cancer with a platinum-free interval >6 months: ENGOT-OV41/GEICO 69-O/ANITA phase Ⅲ trial[J]. J Clin Oncol, 2024, 42(36): 4294-4304. DOI: 10.1200/JCO.24.00668.
[34]	Konstantinopoulos PA, Waggoner S, Vidal GA, et al. Single-arm phases 1 and 2 trial of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma[J]. JAMA Oncol, 2019, 5(8): 1141-1149. DOI: 10.1001/jamaoncol.2019.1048.
[35]	Luo Y, Xia Y, Liu D, et al. Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors[J]. Cell, 2024, 187(18): 4905-4925.e24. DOI: 10.1016/j.cell.2024.06.013.
[36]	Liu S, Deng P, Yu Z, et al. CDC7 inhibition potentiates antitumor efficacy of PARP inhibitor in advanced ovarian cancer[J]. Adv Sci (Weinh), 2024, 11(45): e2403782. DOI: 10.1002/advs.202403782.
[37]	Kamii M, Kamata R, Saito H, et al. PARP inhibitors elicit a cellular senescence mediated inflammatory response in homologous recombination proficient cancer cells[J]. Sci Rep, 2025, 15(1): 15458. DOI: 10.1038/s41598-025-00336-4.
[38]	Shen J, Zhao W, Ju Z, et al. PARPi triggers the STING-dependent immune response and enhances the therapeutic efficacy of immune checkpoint blockade independent of BRCAness[J]. Cancer Res, 2019, 79(2): 311-319. DOI: 10.1158/0008-5472.CAN-18-1003.
[39]	Wang L, Wang D, Sonzogni O, et al. PARP-inhibition reprograms macrophages toward an anti-tumor phenotype[J]. Cell Rep, 2022, 41(2): 111462. DOI：10.1016/j.celrep.2022.111462.

[1]	Jianyong Liu, Yi Jiang. Application of immune checkpoint inhibitors neoadjuvant therapy in liver transplantation for hepatocellular carcinoma[J]. Chinese Archives of General Surgery(Electronic Edition), 2026, 20(02): 127-132.
[2]	Junfeng Zhang, Yue Niu, Peng Chen. Real-world challenges and future directions of neoadjuvant and adjuvant strategies in locally advanced renal cell carcinoma[J]. Chinese Journal of Endourology(Electronic Edition), 2026, 20(03): 248-254.
[3]	Wei Qiao, Qianxin Zhou, Yue Su, Yuan Ma, Sha Zhao. Dynamic immunogenicity analysis of Pneumocystis jirovecii infection prediction in patients with advanced non-small cell lung cancer after immunotherapy[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2026, 19(02): 181-188.
[4]	Yanan Li, Xianghua Huang. Application of vaginal endoscopy in the diagnosis and treatment of female genital tract congenital anomalies[J]. Chinese Journal of Laparoscopic Surgery(Electronic Edition), 2026, 19(02): 77-82.
[5]	Guineng Zeng, Penghui Yang, Rong Liu. Antitumor activity and immune activation effects of recombinant oncolytic influenza virus expressing IL-21 in pancreatic cancer[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2026, 16(03): 129-139.
[6]	Linsen Ye, Yang Yang. Challenges and explorations of advanced liver cancer treatment: review and prospect[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 290-298.
[7]	Zheng Zhou, Shuai Hu, Maoyun Xie, Xiyan Zheng, Ting Liu, Zhiqun Lin, Xianqing Chen, Fei Du, Xianjie Shi. Research progress in perioperative adjuvant therapy for resectable hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 317-325.
[8]	Shengxiong Jia, Yan Xu, Xiaojun He, Kai Tan, Xilin Du. Regulation of CD47-SIRPα axis and CD47 targeted therapy: a new strategy to resolve drug resistance of immunotherapy for pancreatic cancer[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 337-345.
[9]	Sijie Huang, Huiyong Zhang, Xiaohui Guo, Chengrun Xu. Prognostic value of systemic inflammatory response index in patients with advanced liver cancer after TACE combined with targeted immunotherapy[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 355-361.
[10]	Yongqing Ye, Shuaimei Luo, Shunqian Wen, Junpeng Chen, Xianhua Zhang, Liyun Huang, Qijun Lao, Qing Wu. Progress in targeted immunotherapy for intermediate-advanced hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 413-419.
[11]	Wei Xie, Xiaofeng Zhang, Feng Shen. Eepidemiological characteristics, mechanism, prevention and treatment strategies of immune-related adverse events from tumor immunotherapy[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(02): 146-151.
[12]	Chen Wang, Fang Xu, Fang Zhou, Jin Liu, Fang Sheng. Effect of fatty liver disease on clinical efficacy and prognosis of systemic treatment for advanced ICC[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(02): 226-233.
[13]	Jing Zhao, Danling He, Shengjie Hong, Guangquan Zhang, Hanxi He. Prevention and treatment of immune-related skin complications from targeted therapy and immunotherapy for hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(02): 266-270.
[14]	Yichen Zhang, Yuzhou Feng, Chuanqing Bao. Progress of PROTAC in colorectal cancer tumor microenvironment therapy[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2026, 15(02): 175-180.
[15]	Xiumei Chen, Manying Xie, Sijuan Chen, Xuhui Zhong, Qiao Pan, Lijuan Wen, Expert Consensus Writing Group. Expert consensus on nursing management of immune-related adverse events in patients with advanced non-small cell lung cancer[J]. Chinese Journal of Clinicians(Electronic Edition), 2026, 20(02): 77-89.

Viewed

Full text

Abstract

Please choose a citation manager

Content to export