Pertuzumab加Trastuzumab + Docetaxel藥物對轉移性乳腺癌的療效

Pertuzumab加Trastuzumab + Docetaxel藥物對轉移性乳腺癌的療效
Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer
資料來源：http://www.nejm.org/doi/full/10.1056/NEJMoa1113216?query=TOC
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

N Engl J Med 2012; 366:109-119January 12, 2012

背景Background：
抗人類表皮生長因子接受體2型（HER2）的單株抗體藥物 trastuzumab，提升了人類表皮生長因子接受體2型（HER2）陽性的轉移性乳癌患者的療效。
The anti–human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody trastuzumab improves the outcome in patients with HER2-positive metastatic breast cancer. 然而，大多數轉移性乳癌病例，抗人類表皮生長因子接受體2型（HER2）的單株抗體藥物Pertuzumab，會抑制人類表皮生長因子接受體2（HER2）的二聚化（dimerization），對人類表皮生長因子接受體2（HER2）陽性的轉移性乳癌患者，在第2階段臨床試驗，在兩種抗體藥物Trastuzumab + Docetaxel追加和Trastuzumab抗體藥物相輔相成的抗人類表皮生長因子接受體2型（HER2）的單株抗體藥物Pertuzumab，其混合療效是有前瞻性和可接受的藥物安全性。
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.

方法Methods
將人類表皮生長因子接受體2型（HER2）陽性的轉移性乳癌808例患者隨機分配成服用安慰劑加上trastuzumab和docetaxel兩種抗體藥物（對照組），與服用pertuzumab加上trastuzumab和docetaxel兩種抗體藥物（pertuzumab試驗組）接受作為第一線治療，直到進到毒性期無法進行有效管理。
We 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. 主要終點是獨立評估無病變存活期（progression-free survival）。次要終點包括評估總存活期，無病變存活期的調查，有效反應率（objective response rate）和安全評估。
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.

結果Results
安慰劑加上trastuzumab和docetaxel兩種抗體藥物對照組的無病變存活期中位數為 12.4個月，比較pertuzumab加上trastuzumab和docetaxel兩種抗體藥物試驗組的無病變存活期中位數為18.5個月（危險比惡化或死亡，0.62；95％可信賴區間，0.51〜0.75，P <0.001）。
The 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). 整體存活率的中期分析顯示，在pertuzumab加上trastuzumab和docetaxel兩種抗體藥物試驗組的的走勢較強勁。The interim analysis of overall survival showed a strong trend in favor of pertuzumab plus trastuzumab plus docetaxel. 藥物安全性，在兩組相似，無左心室收縮功能不全病例增加； 3級或以上的發熱性嗜中性白血球減少症和腹瀉率，pertuzumab試驗組比安慰劑對照組高。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.

結論Conclusions：
與安慰劑加上trastuzumab和docetaxel兩種抗體藥物對照組做比較，使用pertuzumab加上trastuzumab和docetaxel兩種抗體藥物，作為第一線治療人類表皮生長因子接受體2型（HER2）陽性的轉移性乳腺癌，其混合療效有顯著性延長患者無病變存活期，未增加患者的心臟毒性作用。 （.霍夫曼藥廠F. Hoffmann–羅氏藥廠La Roche /Genentech基因技術公司研發資金；ClinicalTrials.gov美國政府臨床試驗申請編號，NCT00567190）
The 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.)