Jerusalem G, Rorive A, Collignon J
Rev Med Liege. 2014 Sep;69(9):510-7.
Sequential endocrine treatments are recommended for estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER 2) negative metastatic breast cancers except in the case of symptomatic visceral disease. However, patients who suffer from disease progression while receiving a non-steroidal aromatase inhibitor (NSAI) have a very poor prognosis with standard endocrine therapy alone. Recently, based onthe results of the BOLERO 2 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus, combined with exemestane, a steroidal aromatase inhibitor, has been approved in Europe and the US for patients suffering from ER positive HER2 negative advanced breast cancer previously treated by a NSAI. The median progression-free survival (PFS) increased from 3.2 to 7.8 months in patients receiving everolimus and exemestane compared to placebo and exemestane. The magnitude of benefit was consistent in all pre-specified subgroups. Side effects were manageable and the quality of life was at least maintained. Everolimus has also beenrecently studied in HER2 positive locally advanced or metastatic disease in heavily pretreated patients (BOLERO 3 trial). This trial met its primary endpoint. The median PFS was increased in patients receiving trastuzumab, vinorelbine and everolimus compared to patients receiving trastuzumab, vinorelbine and placebo. We review pharmacological data and side effects of the drug. We also review the most important clinical trials leading to reimbursement of everolimus in metastatic breast cancer.
除有症状的内脏疾病外，对于雌激素受体（ER）阳性、人表皮生长因子受体2（HER 2）阴性的转移性乳腺癌，推荐采用序贯内分泌治疗。然而，接受非甾体芳香化酶抑制剂（NSAI）治疗时疾病进展的患者，仅采用标准内分泌治疗预后很差。最近，基于BOLERO 2试验的结果，哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂依维莫司联合甾体芳香化酶抑制剂依西美坦，已在欧洲和美国获批用于先前接受过NSAI治疗的ER阳性、HER2阴性晚期乳腺癌患者。与接受安慰剂和依西美坦的患者相比，接受依维莫司和依西美坦的患者中位无进展生存期（PFS）从3.2个月增至7.8个月。在所有预先设定的亚组中，获益程度均一致。副作用可控，生活质量至少得以维持。最近，依维莫司也在HER2阳性局部晚期或转移性疾病的大量预处理患者中进行了研究（BOLERO 3试验）。该试验达到了其主要终点。与接受曲妥珠单抗、长春瑞滨和安慰剂的患者相比，接受曲妥珠单抗、长春瑞滨和依维莫司的患者中位PFS有所增加。我们回顾了该药物的药理学数据和副作用。我们还回顾了导致依维莫司在转移性乳腺癌中获得报销的最重要临床试验。
