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.).