Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer.
Baselga, Jose M.D., Ph.D.; Cortes, Javier M.D.; Kim, Sung-Bae M.D.; Im, Seock-Ah M.D.; Hegg, Roberto M.D.; Im, Young-Hyuck M.D.; Roman, Laslo M.D.; Pedrini, Jose Luiz M.D.; Pienkowski, Tadeusz M.D.; Knott, Adam Ph.D.; Clark, Emma M.Sc.; Benyunes, Mark C. M.D.; Ross, Graham F.F.P.M.; Swain, Sandra M. M.D.; the CLEOPATRA Study Group *
[Article]
New England Journal of Medicine.
366(2):109-119, January 12, 2012.
(Format: HTML, PDF)
Background: The 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.
Methods: 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. 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.
Results: 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). 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.
Conclusions: 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.)
Copyright (C) 2012 Massachusetts Medical Society. All rights reserved.
