Division of Medical Oncology, University of Toronto and Princess Margaret Hospital, Toronto, Canada.
Cancer Treat Rev. 2010 Aug;36(5):410-5. doi: 10.1016/j.ctrv.2009.12.012. Epub 2010 Jan 25.
In vitro studies have shown that lapatinib is most active in HER2 over-expressing tumors, but also has activity in cell lines over-expressing HER1. Consequently, clinical testing of lapatinib has been carried out in both HER2-positive and HER2-negative patients. Here we evaluate the clinical efficacy of lapatinib in HER2-positive and HER2-negative patients.
A published data meta-analysis of randomized trials that evaluated the efficacy of combining lapatinib with chemo- or endocrine therapy in patients with metastatic breast cancer was undertaken. Hazard ratios (HR) were extracted for progression free survival (PFS) and overall survival, while odds ratios were extracted for disease stabilization, serious adverse events (SAEs) and need for discontinuation. Pooled estimates were computed using inverse-variance and random-effect modeling.
Three randomized controlled trials with a total of 2264 patients met the inclusion criteria. Meta-analysis demonstrated the HR for PFS with lapatinib was 0.69 in patients with HER2-positive disease, while there was no improvement in PFS (HR=0.98, 95% CI 0.80-1.19) for treatment of HER2-negative breast cancer. Similarly, overall survival was improved in HER2-positive patients (HR 0.76, 95% CI 0.60-0.96), but not in HER2-negative patients (HR 0.89, 95% CI 0.65-1.21). Patients on lapatinib were 64% more likely to develop a SAE and 2.3 times more likely to discontinue therapy due to toxicity.
Clinical benefit from treatment with lapatinib is limited to patients with HER2-positive breast cancer. Outside of the clinical trial setting, lapatinib should not be administered to women with HER2-negative disease because it causes increased toxicity without improving disease outcome.
体外研究表明，拉帕替尼在 HER2 过表达的肿瘤中最为活跃，但在过表达 HER1 的细胞系中也具有活性。因此，拉帕替尼的临床测试已经在 HER2 阳性和 HER2 阴性患者中进行。在这里，我们评估拉帕替尼在 HER2 阳性和 HER2 阴性患者中的临床疗效。
对评估拉帕替尼联合化疗或内分泌治疗转移性乳腺癌患者疗效的随机试验进行了已发表数据的荟萃分析。提取无进展生存期（PFS）和总生存期的风险比（HR），提取疾病稳定、严重不良事件（SAE）和停药需要的比值比。使用逆方差和随机效应模型计算汇总估计值。
共有 3 项随机对照试验，共 2264 例患者符合纳入标准。荟萃分析表明，HER2 阳性疾病患者使用拉帕替尼的 PFS 风险比为 0.69，而 HER2 阴性乳腺癌患者的 PFS 无改善（HR=0.98，95%CI 0.80-1.19）。同样，HER2 阳性患者的总生存期得到改善（HR 0.76，95%CI 0.60-0.96），但 HER2 阴性患者则不然（HR 0.89，95%CI 0.65-1.21）。接受拉帕替尼治疗的患者发生 SAE 的可能性增加了 64%，因毒性而停止治疗的可能性增加了 2.3 倍。
拉帕替尼治疗的临床获益仅限于 HER2 阳性乳腺癌患者。在临床试验之外，不应该给 HER2 阴性疾病的女性使用拉帕替尼，因为它会增加毒性而不会改善疾病结局。
