| General information |
| Database: | DB01031 |
| Objective: | lapatinib and bevacizumab as treatment for human epidermal growth factor receptor 2overexpressing metastatic breast cancer. |
| Authors: | Hope S. Rugo |
| Title: | a phase II study of lapatinib and bevacizumab as treatment for human epidermal growth factor receptor 2overexpressing metastatic breast cancer. |
| Journal: | Breast Cancer Research and Treatment |
| Year: | 2012 |
| PMID: | 22198412 |
| Trial Design |
| Clinical Trial Id: | NCT00444535 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | lapatinib and bevacizumab |
| Study Type: | The purpose of this singlearmphase II study was to determine the efficacy and safety of the dualtargeting combination of lapatinib and bevacizumab. |
| Key Patients Feature: | women aged more than and equal to 18 years with histologically confirmed locally advanced stage III/IV breast cancer that overexpressed human epidermal growth factor receptor 2 (either 3+ by immunohistochemistry [IHC] or positive fluorescence in situ hybridization [FISH+]). patients were eligible if they had: an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; adequate hepatic, renal, and hematologic function; and a cardiac ejection fraction within the institutional normal range. Prior anticancer therapy for MBC, including prior human epidermal growth factor receptor 2 and VEGFdirected, was permitted but not required. Women of childbearing potential were required to have a negative serum pregnancy test at baseline and to use appropriate contraception. |
| Biomarker: | human epidermal growth factor receptor 2overexpressing |
| Biomark Analysis: | Lapatinib plus bevacizumab was active in patients with human epidermal growth factor receptor 2overexpressing breast cancer. |
| Control Group Info: | NA |
| Treatment Info: | 1, 500 mg oral lapatinib daily plus 10 mg/kg IV bevacizumab every 2 weeks. |
| Primary End Point: | progression free survival (PFS) at week 12; |
| Secondary End Point: | overall tumor response rate (ORR), clinical benefit rate (CBR), duration of response, timetoresponse, PFS, and safety. Circulating tumor cells (CTC) and circulating endothelial cells (CEC) were measured at baseline and during study treatment as potential response markers. |
| Patients Number: | 52 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | ORR: 13.3%; 95% CI: 5.1, 26.8 |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 24.7 weeks (95% CI: 20.4, 35.1) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events (AEs) included diarrhea, rash, and fatigue; most of these were either grade 1 or 2. Clinical responses were correlated with decreases in CTC and CEC. |
| Conclusions: | The combination of lapatinib and bevacizumab is a promising approach to the treatment of human epidermal growth factor receptor 2overexpressing disease and warrants further investigation in combination with chemotherapy in advanced disease. Identifying reliable markers that predict both resistance to antihuman epidermal growth factor receptor 2 agents and response to antiVEGFR therapies is necessary to optimize this treatment strategy. |