| General information |
| Database: | DB00896 |
| Objective: | To evaluate the efficacy and toxicity of erlotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway |
| Authors: | Dickler MN, et al |
| Title: | a phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer. |
| Journal: | Clin Cancer Res. |
| Year: | 2008 |
| PMID: | 19047117 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | advanced breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | erlotinib + bevacizumab |
| Study Type: | a phase II trial |
| Key Patients Feature: | Patients with histologically confirmed breast carcinoma were eligible if they had Stage IV disease that was stable or progressing after treatment with 1 or 2 chemotherapy regimens. |
| Biomarker: | EGFR expression and mutation |
| Biomark Analysis: | The level of EGFR expression was not predictive of response to therapy. |
| Control Group Info: | single arm |
| Treatment Info: | patients were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o. daily) plus bevacizumab, an antiVEGF antibody (15 mg/kg i.v. every 3 weeks). Patients had one to two prior chemotherapy regimens for metastatic disease. |
| Primary End Point: | response rate by Response Evaluation Criteria in Solid Tumors criteria using a Simon 2stage design. |
| Secondary End Point: | toxicity, time to progression, response duration, and stabilization of disease of > or = 26 weeks. |
| Patients Number: | 38 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | One patient achieved a partial response for 52+ months. Fifteen patients had stable disease at first evaluation at 9 weeks; 4 of these patients had stable disease beyond 26 weeks. |
| Median Time to Progression: | 11 weeks (95% confidence interval, 818 weeks) |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The majority of patients experienced diarrhea (84%; grade 3 in only 3%), skin rash (76%; grade 1 or 2 only), and fatigue (63%; grade 1 or 2 only). Four patients (11%) developed grade 3 hypertension that was controlled by oral medications. Eight patients (21%) experienced mild proteinuria (grade 1, n=6; grade 2, n=2). There were two grade 4 events, thrombosis and myalgia. The myalgia was lotheyr back pain and spasm of ¡°unlikely¡± attribution to the study medications, which ultimately lead to imaging studies that confirmed progression of disease. A total of 5 patients had either a dose delay (n=2) or dose reduction (n=3) of erlotinib because of drugrelated toxicities. Per protocol, there were no dose reductions of bevacizumab, nor did any patients require a dose delay of bevacizumab for drugrelated toxicities. |
| Conclusions: | The combination of erlotinib and bevacizumab was welltolerated but had limited activity in unselected patients with previously treated MBC. Biomarkers are needed to identify those MBC patients likely to respond to antiEGFRHER1 plus antiVEGF therapy. |