Renal cell carcinoma
In July 2009, the US Food and Drug Administration (FDA) granted approval for use of the vascular endothelial growth factor (VEGF) inhibitor bevacizumab (Avastin) in combination with interferon alfa for treatment of patients with metastatic renal cell carcinoma (RCC). Approval was based on results from the BO17705 trial, which demonstrated a 5-month improvement in median progression-free survival (PFS) in the patients treated with bevacizumab. In addition, there were positive published results from the Cancer and Leukemia Group B (CALGB) 90206 trial, a randomized, open-label North American study of bevacizumab plus interferon alfa-2b compared with interferon alfa-2b alone in patients with metastatic RCC. CALGB investigators reported a median progression-free survival (PFS) time of 8.4 months for patients treated with the bevacizumab combination, compared with a PFS time of 4.9 months for patients who received single-agent interferon alfa-2b. An overall survival improvement was not observed. Toxicity with combined bevacizumab and interferon alfa-2b was increased and more severe compared with interferon alfa-2b alone. Proteinuria occurred in 20% of patients with a median onset of 5.6 months, and median time to resolution was 6.1 months.
In May 2009, the FDA approved bevacizumab as a single agent for treatment of patients with glioblastoma progressing despite treatment with other therapies. Glioblastoma multiforme tumors have a high expression of VEGF, which is produced both by the tumor and by the microenvironment, or stroma. While this overexpression is associated with a poor prognosis, it also provides a target that can be blocked by bevacizumab.
Approval of bevacizumab for use in selected patients with glioblastoma was based on the results of two single-arm trials, AVF3708g and NCI 06-C-0064E, that showed durable objective responses to treatment including this drug. AVF3708g was an open-label, randomized multicenter trial in patients previously treated with radiotherapy and temozolomide (Temodar). Patients received bevacizumab
(10 mg/kg IV) alone or with irinotecan every 2 weeks until disease progression or unacceptable toxicity was noted. Only efficacy data from the bevacizumab monotherapy arm (85 patients) were used to support drug approval.
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