NEJM：两种HER2抑制剂联用能显著延长乳腺癌生存期

    研究发现，对于HER2阳性转移性乳腺癌，曲妥珠单抗+多西他赛+培妥珠单抗较曲妥珠单抗+多西他赛+安慰剂治疗可使患者无进展生存期（PFS）中位延长6.1个月。

　　CLEOPATRA（培妥珠单抗联合曲妥珠单抗临床评估）研究是一项随机、双盲、Ⅲ期国际研究，研究中808例患者被随机分为曲妥珠单抗+多西他赛联合培妥珠单抗或安慰剂治疗组。结果显示，培妥珠单抗组和安慰剂组PFS分别为18.5个月和12.4个月，前者进展风险较后者降低38%。

　　12月6-10日举行的圣安东尼奥乳腺癌大会报告了上述结果。哈佛大学医学院高级研究员José Baselga博士说，这一发现对于这种晚期乳腺癌的治疗是显著进步。

　　“这是巨大的进步。临床试验中PFS有如此改善是十分罕见的，” Baselga说，“大部分HER2阳性转移性乳腺癌患者最终会对曲妥珠单抗耐药，因此发现一种添加至当前治疗方案可延缓疾病进展的药物是非常令人兴奋的。随着曲妥珠单抗和培妥珠单抗的相继出现，我们在应对一种先前显示预后很差的乳腺癌方面取得了长足进步。”该研究结果已经发表于《新英格兰医学杂志》（NEJM）。

　　培妥珠单抗组和安慰机组的客观缓解（肿瘤至少缩小30%）率分别为80.2%和69.3%。

　　虽然总的生存状况尚不能进行有效的统计分析，但Baselga已经报告，402例接受三药联合治疗的患者有69例死亡，而406例接受双药治疗的患者有96例死亡。

　　他补充道，三药联合是“非常安全和良好耐受的。添加培妥珠单抗仅有极小副作用。”这些副作用中的一部分如1和2及腹泻和中性粒细胞减少，但并未出现额外的心脏毒性，他说。

英文文献：

Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer

José Baselga, M.D., Ph.D., Javier Cortés, M.D., Sung-Bae Kim, M.D., Seock-Ah Im, M.D., Roberto Hegg, M.D., Young-Hyuck Im, M.D., Laslo Roman, M.D., José Luiz Pedrini, M.D., Tadeusz Pienkowski, M.D., Adam Knott, Ph.D., Emma Clark, M.Sc., Mark C. Benyunes, M.D., Graham Ross, F.F.P.M., and Sandra M. Swain, M.D. for the CLEOPATRA Study Group

BackgroundThe anti–human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody trastuzumab improves the outcome in patients with HER2-positive metastatic breast cancer. However, most cases of advanced disease eventually progress. Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of trastuzumab, and combination therapy with the two antibodies has shown promising activity and an acceptable safety profile in phase 2 studies involving patients with HER2-positive breast cancer
MethodsWe randomly assigned 808 patients with HER2-positive metastatic breast cancer to receive placebo plus trastuzumab plus docetaxel (control group) or pertuzumab plus trastuzumab plus docetaxel (pertuzumab group) as first-line treatment until the time of disease progression or the development of toxic effects that could not be effectively managed. The primary end point was independently assessed progression-free survival. Secondary end points included overall survival, progression-free survival as assessed by the investigator, the objective response rate, and safety.
ResultsThe median progression-free survival was 12.4 months in the control group, as compared with 18.5 months in the pertuzumab group (hazard ratio for progression or death, 0.62; 95% confidence interval, 0.51 to 0.75; P<0.001). The interim analysis of overall survival showed a strong trend in favor of pertuzumab plus trastuzumab plus docetaxel. The safety profile was generally similar in the two groups, with no increase in left ventricular systolic dysfunction; the rates of febrile neutropenia and diarrhea of grade 3 or above were higher in the pertuzumab group than in the control group.
ConclusionsThe combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects. (Funded by F. Hoffmann–La Roche/Genentech; ClinicalTrials.gov number, NCT00567190.)

原始链接：doi:10.1056/NEJMoa1113216

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