日前，發(fā)表于《新英格蘭醫(yī)學(xué)雜志》的研究論文"Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer"表明,，對于HER2陽性轉(zhuǎn)移性乳腺癌,，曲妥珠單抗+多西他賽+培妥珠單抗較曲妥珠單抗+多西他賽+安慰劑治療可使患者無進(jìn)展生存期（PFS）中位延長6.1個月。
CLEOPATRA（培妥珠單抗聯(lián)合曲妥珠單抗臨床評估）研究是一項隨機(jī),、雙盲,、Ⅲ期國際研究，研究中808例患者被隨機(jī)分為曲妥珠單抗+多西他賽聯(lián)合培妥珠單抗或安慰劑治療組,。結(jié)果顯示,，培妥珠單抗組和安慰劑組PFS分別為18.5個月和12.4個月，前者進(jìn)展風(fēng)險較后者降低38%,。
12月6-10日舉行的圣安東尼奧乳腺癌大會報告了上述結(jié)果,。哈佛大學(xué)醫(yī)學(xué)院高級研究員José Baselga博士說,，這一發(fā)現(xiàn)對于這種晚期乳腺癌的治療是顯著進(jìn)步,。
“這是巨大的進(jìn)步。臨床試驗中PFS有如此改善是十分罕見的,，” Baselga說,，“大部分HER2陽性轉(zhuǎn)移性乳腺癌患者最終會對曲妥珠單抗耐藥,，因此發(fā)現(xiàn)一種添加至當(dāng)前治療方案可延緩疾病進(jìn)展的藥物是非常令人興奮的。隨著曲妥珠單抗和培妥珠單抗的相繼出現(xiàn),，我們在應(yīng)對一種先前顯示預(yù)后很差的乳腺癌方面取得了長足進(jìn)步,。”
培妥珠單抗組和安慰機(jī)組的客觀緩解（腫瘤至少縮小30%）率分別為80.2%和69.3%。
雖然總的生存狀況尚不能進(jìn)行有效的統(tǒng)計分析,，但Baselga已經(jīng)報告,，402例接受三藥聯(lián)合治療的患者有69例死亡，而406例接受雙藥治療的患者有96例死亡,。
他補(bǔ)充道,，三藥聯(lián)合是“非常安全和良好耐受的。添加培妥珠單抗僅有極小副作用,。”這些副作用中的一部分如1和2及腹瀉和中性粒細(xì)胞減少,，但并未出現(xiàn)額外的心臟毒性,，他說。(生物谷 Bioon.com)
doi:10.1056/NEJMoa1113216
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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.)
