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在卵巢癌患者中联合 PARP 抑制和免疫检查点阻断:新视角即将出现?

Combining PARP inhibition and immune checkpoint blockade in ovarian cancer patients: a new perspective on the horizon?

机构信息

Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. Electronic address: https://twitter.com/lucia_musacchio.

Department of Medical and Surgical Science, Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. Electronic address: https://twitter.com/carlomcicala.

出版信息

ESMO Open. 2022 Aug;7(4):100536. doi: 10.1016/j.esmoop.2022.100536. Epub 2022 Jul 15.

Abstract

Immune checkpoint inhibitors (ICIs) have completely reshaped the treatment of many malignancies, with remarkable improvements in survival outcomes. In ovarian cancer (OC), however, this emerging class of drugs has not yet found a favorable use due to results from phase I and II studies, which have not suggested a substantial antitumoral activity of these agents when administered as monotherapy. Robust preclinical data seem to suggest that the combination ICIs with poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) may result in a synergistic activity; furthermore, data from phase II clinical studies, evaluating this combination, have shown encouraging outcomes especially for those OC patients not suitable for platinum retreatment. While waiting for ongoing phase III clinical trial results, which will clarify the role of ICIs in combination with PARPis in the newly diagnosed OC, this review aims to summarize the preclinical data and clinical evidence available to date.

摘要

免疫检查点抑制剂 (ICIs) 彻底改变了许多恶性肿瘤的治疗方法,显著提高了患者的生存率。然而,在卵巢癌 (OC) 中,由于 I 期和 II 期研究的结果,这类新兴药物尚未得到广泛应用,这些药物单药治疗时并未显示出明显的抗肿瘤活性。强有力的临床前数据似乎表明,将免疫检查点抑制剂与聚 (ADP-核糖) 聚合酶 (PARP) 抑制剂 (PARPi) 联合使用可能会产生协同作用;此外,评估这种联合用药的 II 期临床研究数据显示出了令人鼓舞的结果,特别是对于那些不适合铂类药物再治疗的 OC 患者。在等待正在进行的 III 期临床试验结果的同时,该结果将阐明 ICIs 联合 PARPi 在新诊断的 OC 中的作用,本文旨在总结目前可用的临床前数据和临床证据。

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