Chen Zhe-Ling, Shen Yan-Wei, Li Shu-Ting, Li Chun-Li, Zhang Ling-Xiao, Yang Jiao, Lv Meng, Lin Ya-Yun, Wang Xin, Yang Jin
Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Onco Targets Ther. 2016 May 30;9:3233-47. doi: 10.2147/OTT.S106055. eCollection 2016.
The addition of human epidermal growth factor receptor 2 (Her2) therapies to neoadjuvant chemotherapy (NAC) during treatment of Her2-positive breast cancer has been proposed as an effective way to improve the prognosis. However, the treatment outcomes of adding trastuzumab, lapatinib, or both to NAC were not unequivocal in randomized clinical trials. Based on these data, a meta-analysis was performed.
The main objective was to evaluate the efficiency and safety of trastuzumab and lapatinib added to NAC for treatment of Her2-positive breast cancer.
ClinicalTrials.gov and PubMed were searched for randomized clinical trials that compared trastuzumab, lapatinib, or both, added to NAC. The main endpoint was a pathologically complete response (pCR) rate, in breast only or in breast and lymph nodes. The drug safety and the influence of hormone-receptor status, comparing the clinical response and the rate of breast conservation, were evaluated.
A total of eight publications were included in the primary analysis, designed as two or three subgroups. The cumulative cases were 2,349 and the analyses of all the clinical trials showed that the pCR rate was significantly higher in the group receiving trastuzumab than that in the group with lapatinib, either in breast only (P=0.001) or in breast and lymph nodes (P=0.0001). Similar results could be seen in comparisons of the combination versus trastuzumab group. Further studies of subgroups divided into hormone receptor-positive or-negative patients showed that the addition of trastuzumab or dual Her2-targeted therapy significantly improved the pCR rate in patients who were hormone-insensitive. Regarding the toxic effects, we found more grade 3 and 4 toxic effects, such as diarrhea, skin disorder, and hepatic biochemical changes in the lapatinib and combination groups. No temporally significant differences were found when the clinical response and the rate of breast conservation in the groups were analyzed.
The combination of trastuzumab and lapatinib was superior to single-agent treatment for improved pCR rate. However, combination treatment was not effective in improving the rate of breast conservation. Furthermore, a higher risk for toxicity was associated with combined administration.
在人表皮生长因子受体2（Her2）阳性乳腺癌治疗中，于新辅助化疗（NAC）期间添加Her2疗法被认为是改善预后的有效方法。然而，在随机临床试验中，将曲妥珠单抗、拉帕替尼或两者添加到NAC中的治疗效果并不明确。基于这些数据，进行了一项荟萃分析。
主要目的是评估在NAC中添加曲妥珠单抗和拉帕替尼治疗Her2阳性乳腺癌的有效性和安全性。
在ClinicalTrials.gov和PubMed上检索比较在NAC中添加曲妥珠单抗、拉帕替尼或两者的随机临床试验。主要终点是仅乳腺或乳腺及淋巴结的病理完全缓解（pCR）率。评估了药物安全性以及激素受体状态的影响，比较了临床反应和保乳率。
共有8篇出版物纳入了初步分析，分为两个或三个亚组。累计病例数为2349例，所有临床试验分析表明，接受曲妥珠单抗治疗的组的pCR率显著高于接受拉帕替尼治疗的组，无论是仅乳腺（P = 0.001）还是乳腺及淋巴结（P = 0.0001）。在联合治疗组与曲妥珠单抗组的比较中也可见类似结果。对分为激素受体阳性或阴性患者的亚组进行的进一步研究表明，添加曲妥珠单抗或双重Her2靶向治疗可显著提高激素不敏感患者的pCR率。关于毒性作用，我们发现在拉帕替尼组和联合治疗组中，有更多3级和4级毒性作用，如腹泻、皮肤疾病和肝脏生化改变。在分析各组的临床反应和保乳率时，未发现时间上的显著差异。
曲妥珠单抗和拉帕替尼联合治疗在提高pCR率方面优于单药治疗。然而，联合治疗在提高保乳率方面无效。此外，联合给药的毒性风险更高。
