Division of Women's Cancers, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
J Neurooncol. 2011 Dec;105(3):613-20. doi: 10.1007/s11060-011-0629-y. Epub 2011 Jun 26.
Approximately one-third of patients with advanced, HER2-positive breast cancer develop brain metastases. A significant proportion of women experience central nervous system (CNS) progression after standard radiation therapy. The optimal treatment in the refractory setting is undefined. This study evaluated the toxicity and efficacy of lapatinib in combination with chemotherapy among patients with HER2-positive, progressive brain metastases. Patients with HER2-positive breast cancer with progressive brain metastases after trastuzumab and cranial radiotherapy were included. The primary endpoint was CNS objective response, defined as a ≥ 50% volumetric reduction of CNS lesion(s) in the absence of new or progressive CNS or non-CNS lesions, or increasing steroid requirements. The study was closed early after 22 of a planned 110 patients were enrolled due to excess toxicity and lack of efficacy in the lapatinib plus topotecan arm. The objective response rate (ORR) in the lapatinib plus capecitabine arm was 38% (exact 95% confidence interval [CI] 13.9-68.4). No responses were observed in the lapatinib plus topotecan arm. Although the study was stopped prior to full enrollment, some promising indications of CNS activity were noted for lapatinib plus capecitabine. The combination of lapatinib plus topotecan was not active and was associated with excess toxicity.
约三分之一的晚期 HER2 阳性乳腺癌患者会发生脑转移。相当一部分女性在标准放射治疗后会出现中枢神经系统（CNS）进展。难治性疾病的最佳治疗方法尚未确定。本研究评估了拉帕替尼联合化疗治疗 HER2 阳性、进展性脑转移的患者的毒性和疗效。HER2 阳性乳腺癌患者在曲妥珠单抗和颅放疗后出现脑转移。主要终点是 CNS 客观缓解，定义为 CNS 病变的体积减少≥ 50%，同时不存在新的或进展性 CNS 或非 CNS 病变，或增加类固醇需求。由于拉帕替尼联合拓扑替康组毒性过大且疗效不佳，该研究在计划入组 110 例患者中的 22 例后提前关闭。卡培他滨联合拉帕替尼组的客观缓解率（ORR）为 38%（确切的 95%置信区间[CI]为 13.9-68.4）。拉帕替尼联合拓扑替康组未观察到任何缓解。尽管该研究在全部入组前提前停止，但卡培他滨联合拉帕替尼显示出了对 CNS 有一定活性的迹象。拉帕替尼联合拓扑替康的组合不具有活性，且与毒性过大相关。
