Xu Zhi-Qiao, Zhang Yan, Li Ning, Liu Pei-Jie, Gao Ling, Gao Xin, Tie Xiao-Jing
Tumor Center, Kaifeng Central Hospital, Kaifeng, China.
BMJ Open. 2017 Mar 13;7(3):e013053. doi: 10.1136/bmjopen-2016-013053.
The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour actively in models of HER2-positive breast cancer. However, the efficacy of trastuzumab in combination with lapatinib remains controversial. Therefore, we conducted this meta-analysis to compare combination treatment with lapatinib and trastuzumab to trastuzumab or lapatinib alone in the treatment of HER2-positive breast cancer.
Randomised controlled trials (RCTs), published in PubMed, Embase and Web of Science, were systematically reviewed to assess the survival benefits and toxicity profile of HER2-positive patients with breast cancer who were treated with lapatinib and trastuzumab. Outcomes included pathological complete response (pCR), event-free survival (EFS), overall survival (OS) and toxicities. Results were expressed as the risk ratio (RR) or HR with 95% CIs. Pooled estimates were calculated by using a fixed-effects model or a randomised-effects model.
A total of 7 RCTs involving 2084 patients met the inclusion criteria and were included in this meta-analysis. The combination of lapatinib and trastuzumab significantly improved pCR (RR=1.43, 95% CI 1.23 to 1.67; p<0.001), EFS (HR=0.75, 95% CI 0.60 to 0.93; p=0.009) and OS (HR=0.72, 95% CI 0.56 to 0.93; p=0.011) in the treatment of HER2-positive breast cancer compared with trastuzumab or lapatinib alone. The combination treatment also increased the pCR irrespective of hormone receptor status and tumour size. More frequent grade 3 or 4 adverse events, including diarrhoea, rash or erythema, neutropenia and hepatic adverse events, were found in the combination group than in the trastuzumab or lapatinib group.
On the basis of the current evidence, our results reveal that the addition of lapatinib to trastuzumab can significantly improve pCR, EFS and OS with a tolerated toxicity in patients with HER2-positive breast cancer. Further well-conducted, large-scale trials are needed to validate these findings.
抗HER2单克隆抗体曲妥珠单抗和酪氨酸激酶抑制剂拉帕替尼具有互补的作用机制，在HER2阳性乳腺癌模型中具有协同抗肿瘤活性。然而，曲妥珠单抗联合拉帕替尼的疗效仍存在争议。因此，我们进行了这项荟萃分析，以比较拉帕替尼与曲妥珠单抗联合治疗与曲妥珠单抗或拉帕替尼单药治疗HER2阳性乳腺癌的疗效。
系统检索PubMed、Embase和Web of Science上发表的随机对照试验（RCT），以评估接受拉帕替尼和曲妥珠单抗治疗的HER2阳性乳腺癌患者的生存获益和毒性特征。结局指标包括病理完全缓解（pCR）、无事件生存期（EFS）、总生存期（OS）和毒性反应。结果以风险比（RR）或风险比（HR）及95%置信区间（CI）表示。采用固定效应模型或随机效应模型计算合并估计值。
共有7项RCT（涉及2084例患者）符合纳入标准并纳入本荟萃分析。与曲妥珠单抗或拉帕替尼单药治疗相比，拉帕替尼与曲妥珠单抗联合治疗显著提高了HER2阳性乳腺癌治疗的pCR（RR=1.43，95%CI 1.23至1.67；p<0.001）、EFS（HR=0.75，95%CI 0.60至0.93；p=0.009）和OS（HR=0.72，95%CI 0.56至0.93；p=0.011）。联合治疗也提高了pCR，且不受激素受体状态和肿瘤大小的影响。联合治疗组比曲妥珠单抗或拉帕替尼组更频繁出现3级或4级不良事件，包括腹泻、皮疹或红斑、中性粒细胞减少和肝脏不良事件。
基于现有证据，我们的结果显示，在HER2阳性乳腺癌患者中，曲妥珠单抗联合拉帕替尼可显著提高pCR、EFS和OS，且毒性可耐受。需要进一步开展设计良好的大规模试验来验证这些发现。
