New indication: Bevacizumab (Avastin), a monoclonal antibody, was approved on July 31, 2009, for the treatment of metastatic renal cell carcinoma in combination with interferon alfa
Bevacizumab is a recombinant humanized monoclonal antibody (mAb) that inhibits the activity of human vascular endothelial growth factor (VEGF), thereby inhibiting angiogenesis. This agent was approved on July 31, 2009, for use in combination with interferon alfa for the treatment of metastatic renal cell carcinoma.
Efficacy. The efficacy of bevacizumab in combination with interferon alfa for the treatment of metastatic renal cell carcinoma was evaluated in a multicenter, randomized, double-blind, international study that compared bevacizumab 10 mg/kg every 2 weeks plus interferon alfa with placebo plus interferon alfa. Patients were treated until disease progression or unacceptable toxicity occurred. The main outcome was investigator-assessed progression-free survival (PFS). In bevacizumab-treated patients, PFS was significantly improved versus placebo-treated patients (median PFS, 10.2 mo vs 5.4 mo; HR=0.6; 95% CI, 0.49–0.72; P<.0001).
Safety. Patients treated with bevacizumab have been more likely to experience gastrointestinal perforation than patients treated with controls in clinical studies. Bevacizumab may impair wound healing; therefore, treatment with this agent should be discontinued for ≥28 days before surgery and should not be initiated or re-initiated for ≥28 days after surgery and until the surgical wound fully heals. Bevacizumab therapy may result in minor or serious, occasionally fatal, hemorrhagic events, including hemoptysis, gastrointestinal bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding. In clinical trials, bevacizumab-treated patients were more likely to experience serious, sometimes fatal nongastrointestinal fistula formation than control-treated patients. Patients treated with bevacizumab in clinical trials have been more likely to experience serious, sometimes fatal arterial thromboembolic events. Bevacizumab is associated with higher rates of severe hypertension than are control drugs; blood pressure should be monitored every 2 to 3 weeks during bevacizumab treatment. Rarely, patients treated with bevacizumab have developed reversible posterior leukoencephalopathy syndrome (RPLS). The incidence and severity of proteinuria are increased among bevacizumab-treated patients versus controls. Infusion reactions, including hypertension, hypertensive crises associated with neurologic signs and symptoms, wheezing, oxygen desaturation, Grade 3 hypersensitivity, chest pain, headaches, rigors, and diaphoresis, have been reported in bevacizumab-treated patients. Immunogenicity may occur among bevacizumab-treated patients. The most common adverse events associated with bevacizumab therapy include epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.