A phase II study of combined VEGF inhibitor (bevacizumab+sorafenib) in patients with metastatic breast cancer: Hoosier Oncology Group Study BRE06-109

Purpose: Angiogenesis plays an essential role in tumor development, invasion and metastasis. We evaluated the efficacy and safety of dual angiogenesis blockade with bevacizumab and sorafenib in patients with metastatic breast cancer. Patients and Methods: Patients who had received no more than 2 prior chemotherapy regimens in any setting were treated with sorafenib 200 mg as a single oral dose daily plus bevacizumab intravenously 5 mg/kg every other week. Response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST). The primary endpoint was progression free survival (PFS). Results: Eighteen patients were enrolled. Median age was 56 yo, all had good performance status KPS of 0 or 1, and 17 patients had received 1 or 2 prior chemotherapy regimens. Median PFS was 2.8 months. There were no complete or partial responses; 3 patients had stable disease for >6 months. Toxicity was substantial with 9 (50 %) patients reporting Grade 3 toxicity. Seven (39 %) patients discontinued therapy due to adverse events including hypertension (N = 2), GI toxicity (N = 1), sensory neuropathy (N = 1), rash (N = 1), pain (N = 1) and wound complication (N = 1). Given the lack of clear efficacy and increased toxicity, accrual was terminated. Conclusion: The combination of sorafenib and bevacizumab has substantial toxicity and minimal efficacy in patients with previously treated metastatic breast cancer. Further study of this combination is not recommended.