a Department of Medical Oncology , BC Cancer, Vancouver Centre , Vancouver , Canada.
Expert Rev Clin Pharmacol. 2018 Sep;11(9):833-839. doi: 10.1080/17512433.2018.1513321. Epub 2018 Aug 30.
Germ line BRCA mutations (gBRCAm) are diagnosed in approximately 5% of unselected breast cancer patients. Olaparib is a new treatment option for patients with a gBRCAm who have metastatic HER2-negative breast cancer. Areas covered: Olaparib is an oral poly (ADP-ribose) polymerase inhibitor that has been shown in phase I-III clinical trials to have single-agent efficacy in breast cancer patients with gBRCAm. The recent phase III OlympiAD study demonstrated a statistically significant progression-free survival benefit compared with the chemotherapy control arm, although an overall survival benefit has not been demonstrated. The most common adverse events seen with olaparib include nausea, anemia, and vomiting. The most common grade 3 adverse events are anemia and neutropenia. Expert commentary: The US FDA-approved olaparib tablets in January 2018 for the treatment of patients with a gBRCAm and metastatic HER2-negative breast cancer. This is a well-tolerated and effective treatment option for this patient population, particularly in patients with triple-negative breast cancer in which chemotherapy is the only alternative. More data are needed to understand the role of olaparib in combination with endocrine therapy, other targeted agents, and chemotherapy, as well as sequentially with platinum chemotherapy in the metastatic setting.
胚系 BRCA 突变（gBRCAm）在未经选择的乳腺癌患者中约占 5%。奥拉帕利是一种新的治疗选择，适用于转移性 HER2 阴性乳腺癌且存在 gBRCAm 的患者。
奥拉帕利是一种口服聚（ADP-核糖）聚合酶抑制剂，在 I-III 期临床试验中已显示出在具有 gBRCAm 的乳腺癌患者中具有单药疗效。最近的 III 期 OlympiAD 研究显示与化疗对照组相比，无进展生存期有统计学意义上的获益，尽管尚未显示出总生存期的获益。奥拉帕利最常见的不良反应包括恶心、贫血和呕吐。最常见的 3 级不良反应是贫血和中性粒细胞减少。
美国 FDA 于 2018 年 1 月批准奥拉帕利片剂用于治疗存在 gBRCAm 和转移性 HER2 阴性乳腺癌的患者。这是该患者人群的一种耐受性良好且有效的治疗选择，特别是对于化疗是唯一选择的三阴性乳腺癌患者。需要更多的数据来了解奥拉帕利在联合内分泌治疗、其他靶向药物以及化疗中的作用，以及在转移性环境中与铂类化疗的序贯应用。
