Medical Oncology Service, Departamento de Medicina, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense, CiberOnc, Madrid, Spain.
Drugs. 2020 Feb;80(2):131-146. doi: 10.1007/s40265-019-01235-5.
The poly-(ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib, have recently been approved for use in patients with metastatic breast cancer (BC) and germline BRCA 1 or 2 mutations due to improved progression-free survival compared to chemotherapy. An increasing number of clinical trials are evaluating the role of PARP inhibitors (PARPi) in BC, alone and in combination with other therapies (including immunotherapy), as well as in earlier stages of the disease. This review describes the unique mechanism of action of these drugs and puts into clinical context the results of pivotal clinical trials. We also discuss the future development of PARPi in BC, their potential combination with other strategies, including chemotherapy and immune-checkpoint inhibitors, and the impact of these treatments in current genetic counselling.
聚(ADP-核糖)聚合酶(PARP)抑制剂奥拉帕利和他拉唑帕利,由于与化疗相比,改善了无进展生存期,最近已被批准用于转移性乳腺癌(BC)和种系 BRCA1 或 2 突变的患者。越来越多的临床试验正在评估 PARP 抑制剂(PARPi)在 BC 中的作用,包括单独使用和与其他疗法(包括免疫疗法)联合使用,以及在疾病的早期阶段。这篇综述描述了这些药物的独特作用机制,并将关键性临床试验的结果置于临床背景下。我们还讨论了 PARPi 在 BC 中的未来发展,它们与其他策略(包括化疗和免疫检查点抑制剂)的潜在联合应用,以及这些治疗方法对当前遗传咨询的影响。