| General information |
| Database: | DB01075 |
| Objective: | Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. |
| Authors: | Jos¨¦ Baselga |
| Title: | Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. |
| Journal: | NEJM |
| Year: | 2012 |
| PMID: | 22149875 |
| Trial Design |
| Clinical Trial Id: | NCT00567190 |
| Agent: | trastuzumab
|
| Target: | Receptor proteintyrosine kinase erbB2
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | Pertuzumab plus trastuzumab plus docetaxel |
| Study Type: | a randomized, doubleblind, placebocontrolled, phase III trial involving patients with human epidermal growth factor receptor IIpositive metastatic breast cancer who had not received chemotherapy or biologic therapy for their metastatic disease. |
| Key Patients Feature: | Eligible patients had locally recurrent, unresectable, or metastatic human epidermal growth factor receptor 2positive breast cancer. human epidermal growth factor receptor 2positive status was confirmed centrally, by means of immunohistochemistry (with 3+ indicating positive status) or fluorescence in situ hybridization (with an amplification ratio more than and equal to 2.0 indicating positive status).21 patients were eligible whether they had measurable disease or nonmeasurable disease. Tumor hormonereceptor status was determined locally. Additional eligibility criteria were an age of 18 years or older, a left ventricular ejection fraction of 50% or more at baseline (determined by echocardiography or multiplegated acquisition scanning), and an Eastern Cooperative Oncology Group (ECOG) performance status22 of 0 or 1 (with 0 indicating that the patient is fully active and able to carry on all predisease activities without restriction and 1 indicating that the patient is restricted in physically strenuous activity but is ambulatory and able to carry out work of a light or sedentary nature). Patients may have received one hormonal treatment for metastatic breast cancer before randomization. Patients may have received adjuvant or neoadjuvant chemotherapy with or without trastuzumab before randomization, with an interval of at least 12 months between completion of the adjuvant or neoadjuvant therapy and the diagnosis of metastatic breast cancer. |
| Biomarker: | human epidermal growth factor receptor 2positive |
| Biomark Analysis: | The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as firstline treatment for human epidermal growth factor receptor 2positive metastatic breast cancer, significantly prolonged progression free survival, with no increase in cardiac toxic effects. |
| Control Group Info: | placebo plus trastuzumab plus docetaxel |
| Treatment Info: | placebo plus trastuzumab plus docetaxel (control group) or pertuzumab plus trastuzumab plus docetaxel (pertuzumab group) as firstline treatment until the time of disease progression or the development of toxic effects that could not be effectively managed. |
| Primary End Point: | independently assessed progression free survival. |
| Secondary End Point: | overall survival, progression free survival as assessed by the investigator, the objective response rate, and safety. |
| Patients Number: | 808 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The objective response rate was 69.3% in the control group, as compared with 80.2% in the pertuzumab group.(95% CI, 4.2 to 17.5; P = 0.001) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 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) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | 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 firstline treatment for human epidermal growth factor receptor 2positive metastatic breast cancer, significantly prolonged progression free survival, with no increase in cardiac toxic effects. |