Department of Hematology/Oncology, Southern California Permanente Medical Group, 9400 Rosescrans Ave, Bellflower, CA, 90706, USA.
Division of Hematology/Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Target Oncol. 2019 Jun;14(3):269-283. doi: 10.1007/s11523-019-00641-9.
Developments in systemic therapies beyond traditional cytotoxic chemotherapy have resulted in an unparalleled number of US Food and Drug Administration approvals in the past 5 years for ovarian, endometrial, and cervical cancer. In this review, we highlight registration trials leading to recent Food and Drug Administration approvals for targeted systemic therapies in advanced gynecologic malignancies, encompassing three classes of agents: the antiangiogenic anti-vascular endothelial growth factor antibody bevacizumab in ovarian and cervical cancer, poly (ADP-ribose) polymerase inhibitors in ovarian cancer, and the immune checkpoint inhibitor pembrolizumab in cervical and endometrial cancer. The addition of bevacizumab to chemotherapy has been approved in frontline and relapsed advanced ovarian cancer, in both platinum-resistant and platinum-sensitive settings. Three poly (ADP-ribose) polymerase inhibitors are approved for women with ovarian cancer. Olaparib and rucaparib are utilized in recurrent germline or somatic BRCA mutated ovarian cancer. Along with a third poly (ADP-ribose) polymerase inhibitor, niraparib, they are also Food and Drug Administration approved as maintenance therapy regardless of BRCA mutation status for patients with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy. More recently, olaparib was approved as maintenance therapy for BRCA mutated ovarian cancer following first-line platinum-based chemotherapy. Pembrolizumab has been approved for relapsed cervical cancer with programmed death ligand 1 positivity and relapsed solid tumors with mismatch repair deficiency, which applies to 30% of endometrial cancers. Together, these therapies represent the advent of personalized medicine in gynecologic malignancies. Additional information is required to determine cost-effective strategies for incorporating these therapies and rational means of sequencing these agents.
在过去的 5 年中，除传统细胞毒性化疗以外的系统治疗方法的发展导致了美国食品和药物管理局（FDA）批准了前所未有的大量卵巢癌、子宫内膜癌和宫颈癌治疗药物。在这篇综述中，我们重点介绍了最近 FDA 批准的用于晚期妇科恶性肿瘤靶向系统治疗的注册试验，涵盖了三类药物：抗血管内皮生长因子单克隆抗体贝伐珠单抗用于卵巢癌和宫颈癌，聚（ADP-核糖）聚合酶抑制剂用于卵巢癌，以及免疫检查点抑制剂帕博利珠单抗用于宫颈癌和子宫内膜癌。贝伐珠单抗联合化疗已被批准用于一线和复发性晚期卵巢癌，包括铂耐药和铂敏感患者。三种聚（ADP-核糖）聚合酶抑制剂被批准用于卵巢癌患者。奥拉帕利和鲁卡帕利用于复发性生殖系或体细胞 BRCA 突变卵巢癌。除了第三种聚（ADP-核糖）聚合酶抑制剂尼拉帕利外，无论 BRCA 突变状态如何，它们也被 FDA 批准用于对铂类化疗有完全或部分反应的复发性卵巢癌患者的维持治疗。最近，奥拉帕利被批准用于一线铂类化疗后 BRCA 突变卵巢癌的维持治疗。帕博利珠单抗已被批准用于程序性死亡配体 1 阳性的复发性宫颈癌和错配修复缺陷的复发性实体瘤，适用于 30%的子宫内膜癌患者。这些治疗方法共同代表了妇科恶性肿瘤个体化医学的出现。需要更多信息来确定纳入这些治疗方法的具有成本效益的策略和合理的药物序贯方案。
