Clinical Trials Research Unit, University of Leeds, Leeds, UK.
St James's Institute of Oncology, St James University Hospital, Leeds, UK.
Clin Oncol (R Coll Radiol). 2020 Oct;32(10):656-664. doi: 10.1016/j.clon.2020.06.003. Epub 2020 Jun 27.
Brain (central nervous system; CNS) metastases occur in 30-50% of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). A substantive evidence base for treatment is lacking, but activity with lapatinib plus capecitabine (lap-cap) has been reported. We compared lap-cap with trastuzumab plus capecitabine (tras-cap) in patients with HER2-positive MBC with CNS metastases previously treated with trastuzumab.
This open-label randomised phase II screening trial aimed to randomise 130 participants over 2 years to receive lap-cap or tras-cap. Eligible patients had HER2-positive MBC with newly diagnosed or recently progressed CNS metastases; previous, or current, treatment included: trastuzumab, a taxane or anthracycline and recent completion of local cranial therapy. The primary end point was time to progression of CNS metastases within the 24-week trial period. Secondary objectives included CNS response rate, progression-free survival, steroid use for CNS symptoms and feasibility of recruitment to a large phase III trial.
Between September 2011 and October 2013, 30 participants were randomised, 16 to lap-cap and 14 to tras-cap. Recruitment to a large phase III trial was determined not to be feasible. At 24 weeks, CNS disease progression was 41.8% (95% confidence interval 16.1-67.5%) in lap-cap and 41.2% (95% confidence interval 12.8-69.6%) in tras-cap arms; progression-free survival was 44.4% (95% confidence interval 18.1-70.8%) in lap-cap and 50.0% (95% confidence interval 20.9-79.1%) in tras-cap arms.
Poor recruitment confirmed that a larger phase III trial would not be feasible and prohibited a preliminary evaluation of the superiority of lap-cap over tras-cap. Descriptive statistics are presented to inform the limited evidence base and future study design.
在人表皮生长因子受体 2（HER2）阳性转移性乳腺癌（MBC）患者中，约有 30-50%会发生脑转移（中枢神经系统；CNS）。目前缺乏针对此类疾病的有效治疗方法，但已有报道称拉帕替尼联合卡培他滨（lap-cap）对此具有一定的疗效。本研究旨在比较 lap-cap 与曲妥珠单抗联合卡培他滨（tras-cap）在先前接受过曲妥珠单抗治疗且伴有 CNS 转移的 HER2 阳性 MBC 患者中的疗效。
这是一项开放标签、随机的 II 期筛选试验，计划在 2 年内入组 130 名患者，接受 lap-cap 或 tras-cap 治疗。入组患者须为 HER2 阳性 MBC 伴新诊断或近期进展的 CNS 转移，此前或目前的治疗方案包括：曲妥珠单抗、紫杉类药物或蒽环类药物，以及近期完成局部颅部放疗。主要终点是 24 周试验期间 CNS 转移的进展时间。次要终点包括 CNS 反应率、无进展生存期、CNS 症状的类固醇使用情况以及大型 III 期试验的入组可行性。
在 2011 年 9 月至 2013 年 10 月期间，共入组了 30 名患者，16 名接受 lap-cap 治疗，14 名接受 tras-cap 治疗。入组大型 III 期试验的可行性被确定为不可行。在 24 周时，lap-cap 组的 CNS 疾病进展率为 41.8%（95%置信区间 16.1-67.5%），tras-cap 组为 41.2%（95%置信区间 12.8-69.6%）；lap-cap 组的无进展生存期为 44.4%（95%置信区间 18.1-70.8%），tras-cap 组为 50.0%（95%置信区间 20.9-79.1%）。
较差的入组率证实了更大规模的 III 期试验是不可行的，并且禁止对 lap-cap 相对于 tras-cap 的优势进行初步评估。本研究仅呈现了描述性统计数据，旨在为有限的证据基础和未来的研究设计提供信息。
