McLachlan Jennifer, Banerjee Susana
a Gynaecology Unit , The Royal Marsden NHS Foundation Trust , London , UK.
Expert Opin Pharmacother. 2016;17(7):995-1003. doi: 10.1517/14656566.2016.1165205. Epub 2016 Apr 4.
Despite recent advances in the management of epithelial ovarian cancer, overall survival rates remain poor, and there is a pressing need to develop novel therapeutic agents and maintenance strategies to improve outcomes for women with this disease. Olaparib, a potent oral poly(ADP-ribose) polymerase (PARP) inhibitor, has demonstrated antitumor activity in women with ovarian cancer, associated with homologous recombination deficiency.
This review outlines the rationale for PARP inhibitor therapy in ovarian cancer and summarizes the efficacy and tolerability data for olaparib to date. Ongoing phase III clinical trials of olaparib in ovarian cancer will be discussed.
There are a number of issues regarding the optimal use of olaparib in ovarian cancer, including the identification of a homologous recombination deficiency signature to predict treatment response, establishment of the optimal treatment setting (maintenance or relapsed disease), and evaluation of cost-effectiveness. Finally, the long term consequences of PARP inhibitors, including the risk of myelodysplasia and acute myeloid leukemia need to be quantified in ongoing large phase III clinical trials.
尽管上皮性卵巢癌的治疗最近取得了进展,但总体生存率仍然很低,迫切需要开发新的治疗药物和维持治疗策略,以改善患有这种疾病的女性的治疗效果。奥拉帕利是一种强效口服聚(ADP-核糖)聚合酶(PARP)抑制剂,已在患有卵巢癌且存在同源重组缺陷的女性中显示出抗肿瘤活性。
本综述概述了PARP抑制剂治疗卵巢癌的基本原理,并总结了迄今为止奥拉帕利的疗效和耐受性数据。还将讨论奥拉帕利在卵巢癌中的正在进行的III期临床试验。
关于奥拉帕利在卵巢癌中的最佳使用存在许多问题,包括识别同源重组缺陷特征以预测治疗反应、确定最佳治疗方案(维持治疗或复发性疾病)以及评估成本效益。最后,PARP抑制剂的长期后果,包括骨髓发育异常和急性髓系白血病的风险,需要在正在进行的大型III期临床试验中进行量化。