| General information |
| Database: | DB01048 |
| Objective: | Trastuzumab Emtansine for human epidermal growth factor receptor 2Positive Advanced Breast Cancer |
| Authors: | Sunil Verma |
| Title: | Trastuzumab emtansine for human epidermal growth factor receptor 2positive advanced breast cancer. |
| Journal: | NEJM |
| Year: | 2012 |
| PMID: | 23020162 |
| Trial Design |
| Clinical Trial Id: | NCT00829166 |
| Agent: | Trastuzumab Emtansine
|
| Target: | human epidermal growth factor receptor 2 and microtubuleinhibitory
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomized, openlabel, international trial involving patients with human epidermal growth factor receptor IIpositive, unresectable, locally advanced or metastatic breast cancer who were previously treated with tras tuz u mab and a taxane. |
| Key Patients Feature: | Eligible patients had documented progression of unresectable, locally advanced or metastatic human epidermal growth factor receptor 2positive breast cancer previously treated with a taxane and trastuzumab. Inclusion criteria were progression during or after the most recent treatment for locally advanced or metastatic disease or within 6 months after treatment for earlystage disease, and a centrally confirmed human epidermal growth factor receptor 2positive status, assessed by means of immunohistochemical analysis (with 3+ indicating positive status), fluorescence in situ hybridization (with an amplification ratio more than and equal to 2.0 indicating positive status), or both. Patients with measurable disease (according to modified RECIST) and those with nonmeasurable disease were included. Other eligibility criteria were a left ventricular ejection fraction of 50% or more (determined by echocardiography or multiplegated acquisition [MUGA] scanning) and an Eastern Cooperative Oncology Group performance status of 0 (asymptomatic) or 1 (restricted in strenuous activity but ambulatory and able to do light work). |
| Biomarker: | human epidermal growth factor receptor 2positive |
| Biomark Analysis: | TDM1 significantly prolonged progression free and overall survival with less toxicity than lapatinib plus capecitabine in patients with human epidermal growth factor receptor 2positive advanced breast cancer previously treated with trastuzumab and a taxane. |
| Control Group Info: | Capecitabine + Lapatinib |
| Treatment Info: | Trastuzumab emtansine (TDM1) or Capecitabine + Lapatinib |
| Primary End Point: | progression free survival assessed by independent review, overall survival, and safety. |
| Secondary End Point: | NA |
| Patients Number: | 991 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The objective response rate was higher with TDM1 (43.6%, vs. 30.8% with la pa ti nib plus cap e ci ta bine; P<0.001) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 9.6 months with TDM1 versus 6.4 months with lapatinib plus capecitabine (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P<0.001) |
| Median OS A vs. C: | (30.9 months vs. 25.1 months; hazard ratio for death from any cause, 0.68; 95% CI, 0.55 to 0.85; P<0.001) |
| Adverse Event(agent arm): | Rates of adverse events of grade 3 or above were higher with la pati nib plus cap e ci ta bine than with TDM1 (57% vs. 41%). The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with TDM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine. |
| Conclusions: | TDM1 significantly prolonged progression free and overall survival with less toxicity than la pa ti nib plus cap e ci ta bine in patients with human epidermal growth factor receptor 2positive advanced breast cancer previously treated with tras tuz u mab and a taxane |