Entry Detail
| General information | |
| Database: | DB01051 |
| Objective: | Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2positive metastatic breast cancer |
| Authors: | Kimberly L. Blackwell |
| Title: | Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2positive metastatic breast cancer: final results from the EGF104900 Study. |
| Journal: | journal of clinical oncology |
| Year: | 2012 |
| PMID: | 22689807 |
| Trial Design | |
| Clinical Trial Id: | NCT00320385 |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | lapatinib + trastuzumab |
| Study Type: | a phase III randomized multicenter openlabel study of lapatinib alone compared with lapatinib plus trastuzumab in patients with human epidermal growth factor receptor IIpositive MBC whose disease had progressed during prior trastuzumab therapy. |
| Key Patients Feature: | Eligible patients were required to have human epidermal growth factor receptor 2positive (locally assessed fluorescence in situ hybridization [FISH] positive or immunohistochemistry [IHC] of 3+) MBC with progression while receiving anthracycline, taxane, and the most recent trastuzumab regimen. Patients with objective disease progression after more than and equal to 4 weeks oflapatinib monotherapy were allowed to cross over to combination therapy. |
| Biomarker: | human epidermal growth factor receptor 2positive |
| Biomark Analysis: | These data demonstrated a significant 4.5month median OS advantage with the lapatinib and trastuzumab combination and support dual human epidermal growth factor receptor 2 blockade in patients with heavily pretreated human epidermal growth factor receptor 2positive MBC |
| Control Group Info: | lapatinib monotherapy |
| Treatment Info: | receive lapatinib monotherapy or lapatinib in combination with trastuzumab. |
| Primary End Point: | investigatorassessed PFS per RECIST 1.0. |
| Secondary End Point: | overall response rate, clinical benefit rate, OS, quality of life, and safety. |
| Patients Number: | 296 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 11.1 weeks with combination therapy compared with 8.1 weeks with lapatinib.(HR, 0.74; 95% CI, 0.58 to 0.94; P= .011) |
| Median OS A vs. C: | 14 months for the combination therapy and 9.5 months for lapatinib alone (HR, 0.74; 95% CI, 0.57 to 0.97; stratified logrankP=.026) |
| Adverse Event(agent arm): | The proportion of patients experiencing adverse events (AEs) was similar in both treatment groups (94% receiving combination therapy v 90% receiving monotherapy). Most AEs with more than and equal to 10% incidence were grade 1 or 2. The most common AEs for both treatments were diarrhea, nausea, rash, fatigue, and vomiting. Although incidence of diarrhea was higher in patients receiving the combination therapy compared with those receiving monotherapy (62% v 48%, respectively), the incidence of grademore than and equal to 3 diarrhea was similar between the two treatment arms (7% v 7%). Rash was noted at a higher incidence in patients receiving monotherapy compared with patients receiving combination therapy (29% v 23%, respectively). |
| Conclusions: | These data demonstrated a significant 4.5month median OS advantage with the lapatinib and trastuzumab combination and support dual human epidermal growth factor receptor 2 blockade in patients with heavily pretreated human epidermal growth factor receptor 2positive MBC |