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
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.
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.
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.