Department of Gynecology and Obstetrics, Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China.
Acta Obstet Gynecol Scand. 2022 Sep;101(9):941-951. doi: 10.1111/aogs.14412. Epub 2022 Jun 25.
Advanced and recurrent gynecological cancers are associated with a poor prognosis and there is still a lack of effective treatments. Immune checkpoint blockade (ICB) therapy is an important element of cancer-targeted therapy and immunotherapy. The programed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) pathways are the two main targets of ICB. In this study, we provide a comprehensive review of clinical evidence concerning ICB therapy in gynecological cancers and discuss future implications. All clinical trials of ICB therapy in gynecological cancers were reviewed. We searched ClinicalTrials.gov to collect data from completed and ongoing clinical trials. The clinical evidence regarding the efficacy of ICB agents in gynecological cancers were discussed. Six phase III clinical trials have reported their results of primary outcomes, and a total of 25 phase II clinical trials have been completed. As revealed in phase III trials, pembrolizumab (a PD-1 antibody) improved the overall survival and progression-free survival in endometrial cancer patients with mismatch repair deficiency and cervical cancer patients with expressions of PD-L1. Based on these findings, pembrolizumab was approved by the Food and Drug Administration and European Medicines Agency as a cancer medication used to treat certain patients with endometrial cancer or cervical cancer. Other PD-1 antibodies, including dostarlimab and cemiplimab, also showed antitumor efficacy in clinical trials. Dostarlimab treatment showed an encouraging response rate in endometrial cancer patients with mismatch repair deficiency. Cemiplimab treatment led to a longer overall survival and a lower risk of death than chemotherapy among patients with recurrent cervical cancer. Three completed phase III trials investigated anti-PD-L1 agents (atezolizumab and avelumab) in the treatment of ovarian cancer. The results were not encouraging. Other strategies of ICB therapy which had showed potential clinical benefit in the treatment of gynecological cancers in early-phase trials need to be further evaluated in late-stage trials. The antitumor efficacy of ICB therapy is promising, and the key to making further progress in the treatment of gynecological cancers is to identify more biomarkers and explore innovative combination treatments with other targeted therapies.
晚期和复发性妇科癌症预后较差，目前仍缺乏有效的治疗方法。免疫检查点阻断（ICB）治疗是癌症靶向治疗和免疫治疗的重要组成部分。程序性细胞死亡蛋白 1（PD-1）和细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）途径是 ICB 的两个主要靶点。本研究对妇科癌症的 ICB 治疗的临床证据进行了全面综述，并探讨了其未来的意义。我们检索了ClinicalTrials.gov 以收集已完成和正在进行的临床试验的数据。讨论了 ICB 药物在妇科癌症中的疗效的临床证据。已经报道了六项 III 期临床试验的主要结果，并且已经完成了总共 25 项 II 期临床试验。III 期试验表明，帕博利珠单抗（一种 PD-1 抗体）改善了错配修复缺陷的子宫内膜癌患者和 PD-L1 表达的宫颈癌患者的总生存期和无进展生存期。基于这些发现，pembrolizumab 被美国食品和药物管理局和欧洲药品管理局批准为癌症药物，用于治疗某些子宫内膜癌或宫颈癌患者。其他 PD-1 抗体，包括 dostarlimab 和 cemiplimab，在临床试验中也显示出抗肿瘤疗效。在错配修复缺陷的子宫内膜癌患者中，dostarlimab 治疗显示出令人鼓舞的反应率。在复发性宫颈癌患者中，与化疗相比，cemiplimab 治疗导致总生存期更长，死亡风险更低。三项已完成的 III 期试验研究了抗 PD-L1 药物（atezolizumab 和avelumab）在卵巢癌治疗中的应用。结果并不令人鼓舞。其他在早期临床试验中显示出对妇科癌症有潜在临床获益的 ICB 治疗策略需要在晚期试验中进一步评估。ICB 治疗的抗肿瘤疗效很有前景，进一步提高妇科癌症治疗水平的关键是确定更多的生物标志物，并探索与其他靶向治疗相结合的创新联合治疗方法。
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