Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study
Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study
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DOI：
10.1016/s1470-2045(12)70432-1
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发表时间：
2013-01-01
期刊：
影响因子：
51.1
通讯作者：
Labbe-Devilliers, Catherine
中科院分区：
文献类型：
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作者：
Bachelot, Thomas;Romieu, Gilles;Labbe-Devilliers, Catherine
背景：30-50%的转移性HER2阳性乳腺癌患者发生脑转移。对于弥漫性脑转移瘤，治疗是基于全脑放射治疗(WBRT)。可用的系统性选择寥寥无几。我们的目标是研究拉帕替尼联合卡培他滨治疗HER2阳性乳腺癌脑转移的疗效。方法在这项单臂2期开放、多中心研究中，符合条件的HER2阳性转移性乳腺癌患者以前没有接受过WBRT、卡培他滨或拉帕替尼治疗。试验周期为21天：患者每天服用拉帕替尼(1250 mg，口服)和卡培他滨(2000 mg/m(2))，从第1天到第14天。主要终点是具有客观中枢神经系统反应的患者的比例，其定义是在没有增加类固醇使用、进行性神经症状和进行性中枢神经系统疾病的情况下，中枢神经系统病变体积缩小50%或更多。所有回答都必须在最初回答4周后确认。疗效分析包括所有接受研究药物的患者，并可根据疗效标准进行评估。这项试验在ClinicalTrials.gov注册，编号NCT00967031。从2009年4月15日到2010年8月2日，我们招募了45名患者，其中44名(98%)可评估疗效，中位随访时间为21.2个月(范围2.2-27.6个月)。29例患者有客观的中枢神经系统反应(65.9%，95%可信区间50.1~79.5)，均为部分反应。在所有接受治疗的45名患者中，22名(49%)出现了与治疗相关的3级或4级不良事件，其中最常见的是9名(20%)患者腹泻和9名(20%)患者出现手足综合征。14名患者(31%)至少有一次严重不良事件；4名患者因毒性而停止治疗。没有发生中毒死亡。解释说，拉帕替尼和卡培他滨联合作为HER2阳性乳腺癌脑转移的一线治疗是有效的。3期试验是有必要的。
Background Brain metastases occur in 30-50% of patients with metastatic HER2-positive breast cancer. In the case of diffuse brain metastases, treatment is based on whole brain radiotherapy (WBRT). Few systemic options are available. We aimed to investigate the combination of lapatinib plus capecitabine for the treatment of previously untreated brain metastases from HER2-positive breast cancer.Methods In this single-arm phase 2, open-label, multicentre study, eligible patients had HER2-positive metastatic breast cancer with brain metastases not previously treated with WBRT, capecitabine, or lapatinib. Tretament was given in 21 day cycles: patients received lapatinib (1250 mg, orally) every day and capecitabine (2000 mg/m(2), orally) from day 1 to day 14. The primary endpoint was the proportion of patients with an objective CNS response, defined as a 50% or greater volumetric reduction of CNS lesions in the absence of increased steroid use, progressive neurological symptoms, and progressive extra-CNS disease. All responses had to be confirmed 4 weeks after initial response. Efficacy analyses included all patients who received the study drugs and were assessable for efficacy criteria. This trial is registered with ClinicalTrials.gov, number NCT00967031.Findings Between April 15, 2009, to Aug 2, 2010, we enrolled 45 patients, 44 (98%) of whom were assessable for efficacy, with a median follow-up of 21.2 months (range 2.2-27.6). 29 patients had an objective CNS response (65.9%, 95% CI 50.1-79.5); all were partial responses. Of all 45 treated patients, 22 (49%) had grade 3 or grade 4 treatment-related adverse events, of which the most common were diarrhoea in nine (20%) patients and hand-foot syndrome in nine (20%) patients. 14 (31%) patients had at least one severe adverse event; treatment was discontinued because of toxicity in four patients. No toxic deaths occurred.Interpretation The combination of lapatinib and capecitabine is active as first-line treatment of brain metastases from HER2-positive breast cancer. A phase 3 trial is warranted.