Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial
Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial
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DOI：
10.1093/annonc/mdt359
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发表时间：
2013-12-01
影响因子：
50.5
通讯作者：
Awada, A.
中科院分区：
文献类型：
--
作者：
de Azambuja, E.;Zardavas, D.;Awada, A.
脑转移（BM）对乳腺癌（BC）提出了临床挑战。拉帕替尼或替莫唑胺在 BM 中显示出活性。我们的研究评估了两种药物的联合治疗对 HER2 阳性 BC 和 BM 患者的治疗效果。纳入了 18 名患者，其中 16 名患者患有复发性或进行性 BM。允许任何类型的既往治疗，并通过钆 (Gd) 增强磁共振成像 (MRI) 评估疾病。主要终点是剂量限制毒性（DLT）的评估和最大耐受剂量（MTD）的确定。次要终点包括客观缓解率、临床获益和缓解持续时间。拉帕替尼-替莫唑胺方案显示出良好的毒性特征，因为无法达到 MTD。最常见的不良事件（AE）是疲劳、腹泻和便秘。 15 名可评估患者中有 10 名实现了疾病稳定。 16名BM患者的估计中位生存时间达到10.94个月（95% CI：1.09-20.79），而中位无进展生存时间为2.60个月[95%置信区间（CI）：1.82-3.37]。拉帕替尼-替莫唑胺组合的耐受性良好。在经过大量预处理的人群中观察到了临床活性的初步证据，如脑损伤中发生的体积减少所表明的那样。
Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM.Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response.The lapatinib-temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09-20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82-3.37].The lapatinib-temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions.