Related Pages Search for Clinical Trials 1 NCI's PDQ® Cancer Clinical Trials Registry. Kidney Cancer Home Page 2 NCI's gateway for information about kidney cancer. Highlights from ASCO 2007 3 A collection of links to material summarizing some of the important clinical trial results announced at the 2007 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

Kidney cancer, bevacizumab ⁴ (Avastin®), interferon alfa. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁵.)

Summary

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.

Source

American Society for Clinical Oncology (ASCO) annual meeting, Chicago, June 2, 2007 (see the meeting abstract ⁶).

Background

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 alpha 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 alpha lived a median of 13 to 14 months.

The Study

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.

Results

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.

(Note: Final results from this trial were subsequently published in the Dec. 22, 2007, issue of the Lancet; see the journal abstract ⁷.)

Comments

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 ⁸) as well as sunitinib and temsirolimus (see related story ⁹).

“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.

Glossary Terms

Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.

Prevention of the growth of new blood vessels.

Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in biological therapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological response modifier therapy, biotherapy, BRM therapy, and immunotherapy.

A biological response modifier (a substance that can improve the body's natural response to infections and other diseases). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -gamma. The body normally produces these substances. They are also made in the laboratory to treat cancer and other diseases.

A statistics term. The middle value in a set of measurements.

A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

Surgery to remove a kidney or part of a kidney. In a partial nephrectomy, part of one kidney or a tumor is removed, but not an entire kidney. In a simple nephrectomy, one kidney is removed. In a radical nephrectomy, an entire kidney, nearby adrenal gland and lymph nodes, and other surrounding tissue are removed. In a bilateral nephrectomy, both kidneys are removed.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called best practice and standard of care.

A type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells. Targeted therapy may have fewer side effects than other types of cancer treatments.