Movement of Poly-ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer.
Movement of Poly-ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer.
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DOI：
10.1007/s40265-020-01382-0
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发表时间：
2020-10
期刊：
影响因子：
11.5
通讯作者：
Westin SN
中科院分区：
文献类型：
--
作者：
Onstad M;Coleman RL;Westin SN
在晚期卵巢癌的一线治疗中使用聚（ADP-核糖）聚合酶（PARP）抑制剂最近已成为一种令人兴奋的策略，有可能改善晚期卵巢癌患者的预后。在这篇文章中，我们回顾了最近发表的四项3期随机对照试验的结果，这些试验评估了PARP抑制剂在卵巢癌（SOLO 1，PRIMA，保拉-1和VELIA）的主要治疗中的应用。总的来说，这些研究表明，在前期环境中维持PARP对BRCA相关卵巢癌患者最有益（风险比范围为0.31至0.44），其次是具有同源重组缺陷的肿瘤患者（风险比范围为0.33至0.57）。所有三项研究均包括所有参与者人群，无论生物标志物状态如何，均能够证明PARP抑制剂的获益。FDA已批准olaparib用于BRCA相关卵巢癌患者的一线维持治疗，niraparib用于所有患者，无论生物标志物状态如何。在确定哪些患者应接受一线维持PARP抑制剂以及使用哪种药物时，需要考虑多种因素，包括FDA适应症、剂量偏好、毒性、每个患者人群的风险与获益以及成本。正在进行的研究进一步探索PARP抑制剂的一线使用，包括PARP抑制剂耐药在复发性环境中的潜在下游效应，将PARP抑制剂与其他抗血管生成药物、免疫抑制剂和PARP抑制剂耐药相关通路的抑制剂联合使用。
The use of poly (ADP-ribose) polymerase (PARP) inhibitors in the front-line management of advanced ovarian cancer has recently emerged as an exciting strategy with the potential to improve outcomes for patients with advanced ovarian cancer. In this article, we review the results of four recently published phase 3 randomized controlled trials evaluating the use of PARP inhibitors in the primary treatment of ovarian cancer (SOLO1, PRIMA, PAOLA-1, and VELIA). Collectively, the studies suggest that PARP maintenance in the upfront setting is most beneficial among patients with BRCA-associated ovarian cancers (hazard ratios range from 0.31 to 0.44), followed by patients with tumors that harbor homologous recombination deficiencies (hazard ratios range from 0.33 to 0.57). All three studies that included an all comer population were able to demonstrate benefit of PARP inhibitors regardless of biomarker status. The FDA has approved olaparib for frontline maintenance therapy among patients with BRCA-associated ovarian cancers, and niraparib for all patients, regardless of biomarker status. In determining which patients should be offered frontline maintenance PARP inhibitors, and which agent to use, there are multiple factors to consider, including FDA indication, dosing preference, toxicity, risks versus benefits for each patient population, and cost. There are ongoing studies further exploring the frontline use of PARP inhibitors, including the potential downstream effects of PARP-inhibitor resistance in the recurrent setting, combining PARP-inhibitors with other anti-angiogenic drugs, immunotherapeutic agents, and inhibitors of pathways implicated in PARP inhibitor resistance.
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影响因子：
51.1
作者：
Pujade-Lauraine, Eric;Ledermann, Jonathan A.;Pautier, Patricia
通讯作者：
Pautier, Patricia
抗肿瘤反应的基线临床预测因素对PARP抑制剂Olaparib在生殖线BRCA1/2突变患有晚期卵巢癌的患者中。
影响因子：
--
作者：
Rafii S;Gourley C;Kumar R;Geuna E;Ern Ang J;Rye T;Chen LM;Shapira-Frommer R;Friedlander M;Matulonis U;De Greve J;Oza AM;Banerjee S;Molife LR;Gore ME;Kaye SB;Yap TA
通讯作者：
Yap TA
影响因子：
64.8
作者：
Ray Chaudhuri A;Callen E;Ding X;Gogola E;Duarte AA;Lee JE;Wong N;Lafarga V;Calvo JA;Panzarino NJ;John S;Day A;Crespo AV;Shen B;Starnes LM;de Ruiter JR;Daniel JA;Konstantinopoulos PA;Cortez D;Cantor SB;Fernandez-Capetillo O;Ge K;Jonkers J;Rottenberg S;Sharan SK;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
11.2
作者：
McCabe, Nuala;Turner, Nicholas C.;Ashworth, Alan
通讯作者：
Ashworth, Alan
DOI：
10.1073/pnas.0806092105
发表时间：
2008-11-04
影响因子：
11.1
作者：
Rottenberg, Sven;Jaspers, Janneke E.;Jonkers, Jos
通讯作者：
Jonkers, Jos