Entry Detail
| General information | |
| Database: | DB01044 |
| Objective: | sorafenib in patients with metastatic breast cancer. |
| Authors: | Giulia Bianchi |
| Title: | Phase II multicenter, uncontrolled trial of sorafenib in patients with metastatic breast cancer. |
| Journal: | Anticancer Drugs |
| Year: | 2009 |
| PMID: | 19739318 |
| Trial Design | |
| Clinical Trial Id: | NCT00101400 |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a multinational, openlabelphase II study |
| Key Patients Feature: | at least 18 years of age; had histologically documented MBC that had progressed after at least one prior chemotherapy regimen for metastatic disease; had progressed after at least one adjuvant hormonal therapy if estrogen/progesterone receptor positive; and were not eligible for, or had refused trastuzumab therapy if human epidermal growth factor receptor 2 (human epidermal growth factor receptor 2) positive. Patients were required to have at least one lesion measurable by computed tomography scan or magnetic resonance imaging according to Modified World Health Organization Tumor Response Criteria; at least 4 weeks since the last cytotoxic chemotherapy treatment; adequate hematologic, hepatic, and renal function; and a life expectancy of at least 12 weeks. |
| Biomarker: | circulating levels of VEGF |
| Biomark Analysis: | Baseline vascular endothelial growth factor levels, levels of soluble epidermal growth factor receptor during treatment and both baseline and changes in soluble human epidermal growth factor receptor 2 levels correlated significantly with clinical outcomes. |
| Control Group Info: | single arm |
| Treatment Info: | oral sorafenib, 400 mg twice daily. |
| Primary End Point: | overall best response; |
| Secondary End Point: | percentage of patients with stable disease for greater than or equal to 16 weeks. |
| Patients Number: | 54 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | No complete response was observed; partial response was observed in one patient (2%) and stable disease for at least 8 weeks in 20 patients (38%). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | For the patient with a partial response, the time to response was 145 days and the duration of response was 256 days. |
| Median OS A vs. C: | Median OS was 259 days (95% confidence interval 177-323 days) |
| Adverse Event(agent arm): | The overall incidence of drugrelated toxicity was 28% grade 1, 43% grade 2, and 19% grade 3. The only grade 4 drugrelated adverse event (2%) consisted of an increase in gglutamyl transpeptidase. The most common drugrelated events were dermatologic, constitutional, and gastrointestinal. The highest event rate occurred during cycle 1. Hypertension and bleeding were rare (1.9 and 3.7%, respectively) and were grade 1 events. |
| Conclusions: | Studies evaluating the combination of sorafenib with agents such as letrozole, anastrozole, exemestane, bevacizumab, vinorelbine, paclitaxel, fulvestrant, and abraxane in the metastatic setting are under way. For the adjuvant treatment of breast cancer, sorafenib is being investigated as a single agent and also in combination with doxorubicin and cyclophosphamide with or without paclitaxel, and epirubicin and cyclophosphamide with or without paclitaxel. |