Bevacizumab (Avastin®) Benefits Some Patients With Advanced Kidney Cancer
Addition of the targeted drug bevacizumab (Avastin®) to interferon alpha staved off disease progression for significantly longer than a placebo in patients with advanced kidney cancer.
American Society for Clinical Oncology (ASCO) annual meeting, Chicago, June 2, 2007. The results from this trial were published in the Dec. 22, 2007, issue of the Lancet; see the journal abstract.
An estimated 51,000 Americans will have been diagnosed with kidney cancer (renal cell carcinoma) in 2006 and about 13,000 people are expected to die of the disease. When diagnosed before it has spread to other organs, kidney cancer may be cured by surgery. In 25 to 30 percent of cases, however, the disease has spread (metastasized) by the time it is diagnosed. The estimated five-year survival rate for patients with metastatic kidney cancer is less than 10 percent.
Growth of blood vessels that feed tumors (a process called angiogenesis) is characteristic of kidney cancer. Bevacizumab (Avastin®) is a monoclonal antibody that is believed to slow the growth of blood vessels in tumors (antiangiogenesis). It is an example of a targeted therapy, which attacks cancer cells while leaving most normal cells alone.
Bevacizumab is currently approved for use with other drugs to treat advanced colorectal and lung cancers, and researchers are exploring its uses in other cancers, as well. In a previous study, bevacizumab delayed disease progression in patients with kidney cancer who had suffered a relapse.
Interferon alpha is a biological therapy that slows tumor growth by boosting the ability of the body’s immune system to fight off cancer. At the time the current study began in 2004, interferon alfa was a standard treatment for advanced kidney cancer, although its effectiveness was modest at best. Patients with advanced kidney cancer who were treated with interferon alfa lived a median of 13 to 14 months.
Participating in this international phase III study were 649 patients with advanced kidney cancer. All of them had had surgery to remove their tumors. For the study they were randomly assigned to receive either bevacizumab plus interferon or a placebo plus interferon. The study was double-blinded, meaning that neither patients nor their doctors knew who was getting bevacizumab and who was getting the placebo.
The study’s principal investigator was Bernard Escudier, M.D., of the Gustave Roussy Institute in Villejuif, France.
Disease progression was delayed nearly twice as long (median of 10.2 months) in patients treated with the bevacizumab combination compared with those in the placebo group (median of 5.4 months). Tumors shrank by at least half in 30.6 percent of patients in the bevacizumab group, compared with 12.4 percent of patients who received a placebo.
Although there was a trend toward longer survival for patients treated with the bevacizumab combination, the follow-up period was too short for the researchers to be certain that the survival difference was not due to chance.
Side effects such as fatigue, high blood pressure, and protein in the urine occurred more often in patients treated with bevacizumab, but were rarely severe.
On the basis of these findings, an independent group monitoring the study decided that all patients in the placebo group should be offered the bevacizumab therapy.
This study’s findings suggest that bevacizumab adds to the effectiveness of interferon in patients with metastatic kidney cancer, said Ronald Bukowski, M.D., of the Cleveland Clinic Taussig Cancer Center in Cleveland, Ohio, commenting on the study at the ASCO meeting. Bevacizumab is the fourth new drug within the last two years to show a benefit in this disease, he noted, the others being sorafenib (see related story) as well as sunitinib and temsirolimus.
“We are clearly now seeing a new treatment paradigm for advanced kidney cancer,” Bukowski said.
Most of the benefit of adding bevacizumab was seen in patients with an intermediate or good outlook, Bukowski added, while for patients with a poor outlook the benefit was less clear.
The challenge today is to determine how best to use the spectrum of new antiangiogenesis agents that are active in metastatic disease, but not curative, said Alison Martin, M.D., of the National Cancer Institute’s Cancer Therapy Evaluation Program. Ongoing trials are asking whether combinations are better than single agents, or whether single agents used as adjuvant therapy after nephrectomy can cure patients at high risk for recurrence.