Madariaga Ainhoa, Bowering Valerie, Ahrari Soha, Oza Amit M, Lheureux Stephanie
Medical Oncology & Hematology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada.
Pharmacy, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada.
Int J Gynecol Cancer. 2020 Jul;30(7):903-915. doi: 10.1136/ijgc-2020-001288. Epub 2020 Apr 9.
Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have transformed the treatment landscape in front-line and recurrent high-grade serous ovarian cancer. Maintenance strategies with PARPi have been assessed in randomized phase III trials in ovarian cancer; switch maintenance in the case of olaparib, niraparib, and rucaparib; and concurrent followed by continuation maintenance with veliparib. These studies have shown progression-free survival advantage with PARPi maintenance, with no major adverse changes in the quality of life; however, overall survival data remain immature to date. PARPi have also been incorporated in clinical practice as a single-agent treatment strategy in high-grade serous ovarian cancer, mainly in women who harbor alterations in the genes or have alterations in the homologous recombination deficiency (HRD) pathway. Contemporary studies are looking into potentially synergistic combination strategies with anti-angiogenics and immune checkpoint inhibitors, among others. The expansion of PARPi treatment has not been limited to ovarian cancer; talazoparib is licensed in patients with HER2-negative breast cancer with germline mutations (m), and front-line olaparib maintenance in patients with pancreatic cancer with germline m. Numerous studies assessing PARPi either in monotherapy or in combination with other agents are ongoing in multiple tumors, including prostate, endometrial, brain, and gastric cancers. Many patients are being treated with PARPi, some for prolonged periods of time. As a result, a thorough knowledge of the potential short- and long-term adverse events and their management is warranted to improve patient safety, treatment efficacy, and towards maintaining an appropriate dose intensity.
聚(ADP - 核糖)聚合酶(PARP)抑制剂(PARPi)已经改变了一线和复发性高级别浆液性卵巢癌的治疗格局。PARPi的维持治疗策略已在卵巢癌的随机III期试验中进行了评估;奥拉帕尼、尼拉帕尼和鲁卡帕尼用于转换维持治疗;维利帕尼用于同步治疗后继续维持治疗。这些研究表明,PARPi维持治疗可带来无进展生存优势,且生活质量无重大不良变化;然而,迄今为止总生存数据仍不成熟。PARPi也已作为高级别浆液性卵巢癌的单药治疗策略纳入临床实践,主要用于携带 基因改变或同源重组缺陷(HRD)途径改变的女性。当代研究正在探索与抗血管生成药物和免疫检查点抑制剂等潜在的协同联合策略。PARPi治疗的扩展并不局限于卵巢癌;他拉唑帕尼已获批用于治疗携带胚系 突变(m)的HER2阴性乳腺癌患者,奥拉帕尼用于携带胚系m的胰腺癌患者的一线维持治疗。多项评估PARPi单药治疗或与其他药物联合治疗的研究正在多种肿瘤中进行,包括前列腺癌、子宫内膜癌、脑癌和胃癌。许多患者正在接受PARPi治疗,有些患者接受治疗的时间较长。因此,有必要全面了解潜在的短期和长期不良事件及其管理方法,以提高患者安全性、治疗效果,并维持适当的剂量强度。