The U.S. Food and Drug Administration (FDA) has approved the antiangiogenic drug bevacizumab (Avastin), in combination with interferon-alpha, a type of immunotherapy, for people with metastatic renal cell carcinoma, the most common form of kidney cancer. According to the American Cancer Society, kidney cancer is the eighth most commonly diagnosed cancer in the United States. In 2009, approximately 57,760 Americans will be diagnosed with kidney cancer, and nearly 13,000 will die from the disease1.

Kidney cancer is the uncontrolled growth of cancerous cells that originate in the kidneys without a known cause. Nine out of 10 people with kidney cancer have renal cell carcinoma. Malignant kidney tumors churn out high amounts angiogenic growth factors, which stimulate the growth of new blood vessels (angiogenesis) that provide the tumors with oxygen and micronutrients. Bevacizumab, a monoclonal antibody, blocks VEGF (vascular endothelial growth factor), the primary mediator of angiogenesis in solid tumors, including renal cell carcinoma. Three other inhibitors of angiogenesis—sorafenib (Nexavar), sunitinib (Sutent), and temsirolimus (Torisel)—are approved to treat advanced kidney cancer, but target different parts of the angiogenesis process.

The approval of bevacizumab is based on results from a global phase 3 study (AVOREN) involving 649 patients with previously untreated metastatic renal cell carcinoma2. The study showed that patients who received bevacizumab with interferon-alfa lived about 5 months longer without their disease worsening, known as progression-free survival (PFS), compared to those who received interferon-alfa alone. Patients who received the bevacizumab-interferon-alpha combination had a median PFS of 10.4 months, compared to 5.5 months for patients who only received interferon-alfa.

The study was originally designed to measure an improvement in overall survival (OS). However, in prior consultation with the FDA and European regulatory authorities, the primary analysis endpoint was revised to assess improvement in PFS. In the final analysis, there was no statistically significant improvement in OS, with a median OS of 23 months in the bevacizumab-interferon-alfa combination arm, and 21 months in the interferon-alfa plus placebo arm. Tumors shrank by 31% in patients in the combination group, compared to 12% of patients who received interferon-alfa alone.

The most common bevacizumab-related toxicities were bleeding/hemorrhage, hypertension, protein in the urine (proteinuria), and venous or arterial thromboembolic events. Severe adverse events that were at least 2% more frequent in patients who received bevacizumab plus interferon-alfa compared to interferon-alpha alone included fatigue, weakness, proteinuria, hypertension, and bleeding.