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我是如何用PARP抑制剂治疗卵巢癌病人的

How I Am Using PARP Inhibitors in the Care of Patients With Ovarian Cancer
我是如何用PARP抑制剂治疗卵巢癌病人的
1001字
2019-07-18 15:01
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火星译客

During the past few years, the discovery that PARP inhibitors have activity in BRCA-mutated cancers has been translated into therapeutic strategies for ovarian cancer. Currently, 3 PARP inhibitors are FDA approved as single agents in ovarian cancer: olaparib, rucaparib, and niraparib. The advent of PARP inhibitors is dramatically changing the treatment landscape of ovarian cancer. In this commentary, I take a brief look at the data and clinical relevance of these new agents.

在过去几年中,PARP 抑制剂被发现适合用于治疗BRCA突变的卵巢癌患者。现在,FDA批准了3种PARP抑制剂可单独用于治疗卵巢癌。它们分别是:奥拉帕尼,卢卡帕尼和尼拉帕尼。PARP 抑制剂的到来戏剧化地改变了卵巢癌的治疗前景。在此篇评论中,我将简要介绍这一新药的数据与临床的相关性。

Current Indications and Ongoing Trials

目前的适应症与正在进行的试验

Three phase III trials have demonstrated benefit for PARP inhibitors vs placebo as maintenance therapy for patients with recurrent, platinum-sensitive ovarian cancer: SOLO‑2 (olaparib), NOVA (niraparib), and ARIEL3 (rucaparib). All 3 drugs have now been FDA approved for that indication regardless of BRCA mutation status, although patients with BRCA mutations have seen more robust benefit from PARP inhibitors.

三个三期试验显示PARP抑制剂相较于安慰剂,作为复发合并铂类敏感的卵巢癌患者的维持治疗具有临床获益。SOLO-2(奥拉帕尼),NOVA(尼拉帕尼),和ARIEL3(卢卡帕尼)。所有3种药物都被FDA批准用于治疗卵巢癌患者 (无论BRCA是否突变),尽管BRCA突变的病人在接受PARP抑制剂治疗中会有更有效。

In addition to their use as maintenance therapy, single‑agent PARP inhibitors have been investigated in women with ovarian cancer who are even more heavily pretreated and have underlying BRCA mutations. Olaparib was originally approved by the FDA in patients with recurrent ovarian cancer and germline BRCA mutations who received at least 3 prior lines of treatment. Likewise, rucaparib originally received FDA approval for patients with recurrent ovarian cancer and germline and/or somatic BRCA mutations who received 2 or more prior lines of therapy.

除了被用于维持治疗外,PARP 抑制剂单药亦适用于经过多线治疗或者潜在BRCA突变的卵巢癌患者。奥拉帕尼起初被FDA批准用于复发转移性合并干细胞基因BRCA突变的卵巢癌复发患者,并且这些患者都接受了至少三线的治疗。同样,卢卡帕尼起初被FDA批准用于复发转移性合并干细胞基因或者体细胞突变的卵巢癌患者并且这些患者至少接受了二线及以上的治疗。

In December 2018, the FDA expanded the indication of olaparib to include maintenance treatment for newly diagnosed patients with advanced BRCA-positiveovarian cancer after first-line chemotherapy. The new approval was based on results from the phase III SOLO‑1 study, which demonstrated that olaparib resulted in a 70% reduction in the risk of progression or death vs placebo. Currently, niraparib and rucaparib are being studied as first-line maintenance therapy for newly diagnosed ovarian cancer in the ongoing phase III PRIMA and ATHENA trials, respectively, and the phase III FIRST trial is looking at niraparib plus a PD-1 antibody vs chemotherapy as first-line therapy in ovarian cancer. It's an incredibly exciting time as we wait for these trials to mature and report out.

2018年12月,FDA扩大了奥拉帕尼的适应症,将奥拉帕尼用于继一线化疗后,首次确诊的BRCA阳性进展期卵巢癌患者。这一批准是基于SOLO-1三期试验,即奥拉帕尼相较于安慰剂降低了70%的进展或死亡风险。目前,正在进行的PRIMA和ATHENA试验中,尼拉帕尼和卢卡帕尼正各自作为新诊卵巢癌患者的一线维持治疗药物进行研究。并且三期第一项试验是观察尼拉帕尼联合PD-1相比于化疗作为一线治疗在卵巢癌患者中的疗效。我们翘首期盼这些试验的最终结果,真是令人难以置信且兴奋的时刻。

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    火星译客
    jiong
    3个月前
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    PARP抑制剂是一种能够影响癌细胞的自我复制方式的医学用剂

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