曲妥珠单抗＋拉帕替尼＋新辅助化疗用于HER2阳性乳腺癌患者的有效性和安全性：随机研究荟萃分析

　　2016年5月30日，英国德孚医药出版社旗下《肿瘤标靶与疗法》正式发表中国西安交通大学第一附属医院对8项随机研究（CHER-LOB、EORTC10054、Holmes et al、GEICAM、GeparQuinto、GBG44、NeoALTTO、NSABP、CALGB40601）2349例患者的荟萃分析，发现曲妥珠单抗＋拉帕替尼与曲妥珠单抗单药治疗相比，病理学完全有效率显著提高，无论对于乳腺（P＜0.0001）还是对于乳腺和淋巴结（P＜0.00001），该作用主要见于激素受体阴性（P=0.0001，P=0.03）和激素受体状态未分类（P=0.02，P＜0.0001）患者。但是，联合治疗对提高临床有效率（P=0.14）和保乳率（P=0.73）无显著统计学意义，且3和4级毒性反应发生率较高，例如腹泻、皮肤异常、肝脏生化指标改变。

Onco Targets Ther. 2016 May 30;9:3233-47.

The efficiency and safety of trastuzumab and lapatinib added to neoadjuvant chemotherapy in Her2-positive breast cancer patients: a randomized meta-analysis.

Chen ZL, Shen YW, Li ST, Li CL, Zhang LX, Yang J, Lv M, Lin YY, Wang X, Yang J.

Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

BACKGROUND: 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.

OBJECTIVE: The main objective was to evaluate the efficiency and safety of trastuzumab and lapatinib added to NAC for treatment of Her2-positive breast cancer.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

KEYWORDS: breast cancer; human epidermal growth factor receptor; lapatinib; neoadjuvant; pathologically complete response; trastuzumab

PMID: 27313469

DOI: 10.2147/OTT.S106055