随机试验荟萃分析：拉帕替尼＋曲妥单抗双阻断对比曲妥珠单抗单药联合化疗新辅助治疗HER2阳性乳腺癌

　　2016年5月2日，美国癌症研究协会官方期刊《临床癌症研究》在线发表了意大利加列拉医院的随机试验荟萃分析。

　　该荟萃分析发现，在6项随机试验共1155例患者中，483例（41.8%）激素受体阴性，672例（58.2%）激素受体阳性，534例（46.2%）接受过紫杉类单药化疗，621例（53.8%）接受过蒽环类＋紫杉类或多西他赛＋卡铂方案化疗；拉帕替尼＋曲妥单抗双阻断与曲妥珠单抗单药相比，病理学完全缓解（pCR）率显著提高了13%（总风险差[SRD]：13%，95% CI：0.08～0.19）；接受过紫杉类单药化疗的激素受体阴性患者pCR率更显著提高了25%（SRD：25%，95% CI：0.13～0.37），激素受体阳性或接受过蒽环类＋紫杉类或多西他赛＋卡铂方案化疗的激素受体阴性患者pCR率仅提高了9%（SRD：9%，95% CI：0.02～0.15，P：0.05）。

　　因此，根据pCR变化数据，拉帕替尼＋曲妥单抗双阻断＋化疗是非常有效的治疗，尤其对于经过紫杉类单药治疗的HER2阳性且激素受体阴性乳腺癌。

Clin Cancer Res. 2016 May 2. [Epub ahead of print]

Dual block with lapatinib and trastuzumab versus single agent trastuzumab combined with chemotherapy as neoadjuvant treatment of HER2-positive breast cancer: a meta-analysis of randomized trials.

Clavarezza M, Puntoni M, Gennari A, Paleari L, Provinciali N, D'amico M, De Censi A.

Galliera Hospital (E.O. Ospedali Galliera).

PURPOSE: (Neo)adjuvant treatment with chemotherapy plus trastuzumab reduces recurrence and death risk in HER2-positive breast cancer. Randomized trials assessed HER2 dual block by adding lapatinib to trastuzumab and chemotherapy in the neoadjuvant setting using pathological complete response (pCR) as the outcome measure. We conducted a meta-analysis of randomized trials testing neoadjuvant dual block with lapatinib and trastuzumab versus trastuzumab alone in HER2-positive breast cancer.

EXPERIMENTAL DESIGN: Trials were identified by Medline (PUBMED), ISI Web of Science (Science Citation Index Expanded), Embase, Cochrane library and a reference lists of published studies, review articles, editorials and by hand-searched reports from major cancer meeting reports.

RESULTS: Six randomized trials including 1155 patients were identified, of whom 483 (41.8%) were hormone receptors negative, 672 (58.2%) hormone receptors positive, 534 (46.2%) received taxanes alone and 621 (53.8%) anthracyclines plus taxanes or the docetaxel-carboplatin regimen. Overall, the dual block was associated with a significant 13% absolute improvement in pCR rate compared to single agent trastuzumab (Summary Risk Difference, SRD 0.13; 95%CI: 0.08 to 0.19). The activity was greater in hormone receptors negative patients who received chemotherapy with taxanes alone (SRD 0.25; 95%CI: 0.13 to 0.37), compared to hormone receptors positive or hormone receptors negative disease treated with anthracyclines plus taxanes or the docetaxel-carboplatin regimen (SRD 0.09; 95%CI: 0.02 to 0.15; p-interaction 0.05).

CONCLUSIONS: Based on ΔpCR data, the dual block with trastuzumab and lapatinib plus chemotherapy is a very active treatment only in HER2-positive and hormone receptors negative breast cancer treated with taxane monochemotherapy.

PMID: 27140927

PII: clincanres.1881.2015

DOI: 10.1158/1078-0432.CCR-15-1881