Caruso Giuseppe, Tomao Federica, Parma Gabriella, Lapresa Mariateresa, Multinu Francesco, Palaia Innocenza, Aletti Giovanni, Colombo Nicoletta
Department of Maternal and Child Health and Urological Sciences, University of Rome La Sapienza, Rome, Italy
Department of Experimental Medicine, University of Rome La Sapienza, Rome, Italy.
Int J Gynecol Cancer. 2023 Apr 3;33(4):431-443. doi: 10.1136/ijgc-2022-004149.
Poly (ADP-ribose) polymerase inhibitors (PARPi) represent a new standard of care in the upfront treatment of advanced epithelial ovarian cancer to the point that the vast majority of patients now receive a PARPi, alone or in combination with the anti-angiogenic bevacizumab, as part of their first-line maintenance therapy. The clinical benefit of PARPi is well established; however, much has changed since their introduction and several relevant questions have been raised and remain unresolved in the post-PARPi era. The decision-making process regarding the most appropriate first-line maintenance therapy could be challenging in clinical practice, especially in the homologous recombination-proficient setting, and several other factors need to be considered apart from the mutational status. Concerns regarding post-PARPi progression treatment have emerged, highlighting an unmet need to define a valid algorithm strategy. PARPi may not only compromise the response to further platinum due to cross-resistance mechanisms but the impact on subsequent non-platinum chemotherapy and surgery also remains unclear. Definitive results on the role of PARPi rechallenge are awaited, especially in the case of oligoprogression managed with locoregional treatment. Moreover, the updated overall survival data from the recurrent setting warrant caution in using PARPi as single agents for unselected patients. Several PARPi combination regimens are emerging for overcoming PARPi resistance and may become our new therapeutic armamentarium. This review discusses a set of clinically relevant issues in the PARPi era and provides a glimpse of future challenges and opportunities in ovarian cancer treatment.
聚（ADP - 核糖）聚合酶抑制剂（PARPi）已成为晚期上皮性卵巢癌一线治疗的新标准，以至于现在绝大多数患者在一线维持治疗中单独或联合抗血管生成药物贝伐单抗接受PARPi治疗。PARPi的临床益处已得到充分证实；然而，自其问世以来情况发生了很大变化，在PARPi时代之后出现了几个相关问题且仍未得到解决。在临床实践中，关于最合适的一线维持治疗的决策过程可能具有挑战性，尤其是在同源重组 proficient 环境中，除了突变状态外还需要考虑其他几个因素。关于PARPi治疗后进展治疗的担忧已经出现，凸显了定义有效算法策略的未满足需求。PARPi不仅可能由于交叉耐药机制而损害对进一步铂类药物的反应，而且对后续非铂类化疗和手术的影响也仍不清楚。PARPi再挑战作用的明确结果有待观察，特别是在采用局部区域治疗管理的寡进展情况下。此外，复发环境中更新的总生存数据提醒我们在将PARPi作为未选择患者的单一药物使用时要谨慎。几种PARPi联合方案正在出现以克服PARPi耐药性，可能成为我们新的治疗手段。本综述讨论了PARPi时代一系列临床相关问题，并对卵巢癌治疗未来的挑战和机遇进行了展望。
