Data support its use as part of first-line treatment for advanced renal cell carcinoma.


CHICAGO—Adding bevacizumab (Avastin) to interferon as a first-line therapy for advanced renal cell carcinoma (RCC) nearly doubles progression-free survival, phase III trial data suggest. It is unclear whether it boosts overall survival.

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In the AVOREN trial, patients who received bevacizumab and interferon alpha-2a had a mean progression-free survival of 10.2 months compared with only 5.4 months in patients who received interferon alone. In addition, tumor response increased significantly from 12.8% in the interferon monotherapy group to 31.4% in combination arm.


Bevacizumab is approved in the United States for the treating advanced colorectal cancer and non-small cell lung cancers. It is being evaluated as a treatment for a number of other tumor types. The AVOREN trial is the first randomized phase III trial to confirm its efficacy as first-line treatment for advanced RCC.


“These results are significant because there is a real need for more effective treatments in advanced kidney cancer, where chemotherapy and radiotherapy are not as effective as in other cancers,” said principal investigator Bernard Escudier, MD, head of the immunotherapy unit at Gustave Roussy Institute in Paris. “Bevacizumab has been shown to be efficacious and well tolerated and is an important new treatment option in the fight against this cancer.” He presented study findings here at study findings presented at the American Society of Clinical Oncology annual meeting.


The AVOREN trial also showed a trend toward improved overall survival, but the results of survival analyses are pending. Researchers observed no new or unexpected adverse events associated with bevacizumab.


The trial was a double-blind study of 649 patients from 101 study sites across 18 countries. Patients received either interferon alpha-2a plus placebo or interferon alpha-2a plus bevacizumab. The primary end point was overall survival when bevacizumab was added to interferon therapy. Secondary end points include progression-free survival, time to progression, time to treatment failure, overall response rate, and safety profile.


Dr. Escudier said the benefits of bevacizumab shown during the trial were so positive that based on earlier interim results in December 2006, the Drug Safety Monitoring Board recommended that the trial be unblinded and all patients be offered treatment with this agent after December 2006.


Historically, there have been few treatment options for this patient population. In the past 18 months, two therapies shown to increase survival in patients have received FDA approval: sorafenib (Nexavar) and sunitinib (Sutent). With the availability of these two agents, interferon is no longer considered the standard for RCC patients, Dr. Escudier said.


Additional studies are likely to test bevacizumab as a single agent for first-line therapy by directly comparing it against sorafenib and sunitinib, as well as evaluating it in combination with those drugs and the experimental drug temsirolimus.


“We’re in a very exciting time in kidney cancer research, with a number of new targeted therapies becoming available,” Dr. Escudier said.  “This study shows the efficacy of yet another agent, with the added benefit of a strong safety profile.”


Severe side effects in this study were infrequent and included fatigue (12% in the bevacizumab group vs. 8% in the placebo group), loss of strength (10% vs.7%) and proteinuria (7% vs. 0%).

Bevacizumab inhibits angiogenesis and it specifically targets a nat-urally occurring protein called vascular endothelial growth factor, a key mediator of angiogenesis. To date, bevacizumab has demonstrated a progression-free and/or overall survival benefit for patients with colorectal, breast, lung, and renal cancer. Ongoing trials continue to examine the drug’s efficacy as a stand-alone.