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New Drugs Unleash Immune System to Attack Tumors

Lung, Skin, Kidney Tumors Shrink in Early-Stage Trials

By Charlene Laino
WebMD Health News

Reviewed by Laura J. Martin, MD

June 4, 2012 (Chicago) -- Two experimental drugs that recharge the body's immune system to seek out and attack tumors are showing promise for the treatment of certain advanced lung, skin, and kidney cancers.

The drugs disable a molecular shield that tumors put up to block attacks from the immune system. In early-stage studies, the drugs shrank tumors in some people with certain types of lung, skin, and kidney cancers who had not been helped by other treatments.

Researcher Julie Brahmer, MD, associate professor of oncology at Johns Hopkins Kimmel Cancer Center, tells WebMD that she is optimistic because "in some patients, tumors did not grow back even after treatment was stopped."

"These patients had been through several types of therapy and were very ill," she says.

It's too soon to say whether the drugs will extend lives and whether they are safe in the long run. A larger, longer study is planned to test that.

But the early studies suggest the drugs work at least as well as chemotherapy drugs currently in use, and possibly with fewer side effects, Brahmer says.

The research was presented here at the annual meeting of the American Society of Clinical Oncology and published online by the New England Journal of Medicine. Both drugs are made by Bristol-Myers Squibb, which helped fund the work.

Immune Drugs: How They Work

One of the new drugs blocks a protein called programmed death-1 (PD-1) that sits on the surface of immune cells. The other drug blocks a protein called programmed death ligand-1 (PD-L1) that is on the surface of cancer cells. When PD-1 and PD-L1 join together, they form a biochemical shield that protects tumor cells from the immune system.

"We showed that blocking either of these proteins works to get tumor shrinkage," Brahmer says.

The PD-1-blocking drug was tested in about 250 patients with various advanced cancers who had not responded to standard therapies. Tumors shrank by 50% or more in 14 of 76 (18%) non-small-cell lung cancer patients, 26 of 94 (28%) patients with the potentially deadly skin cancer melanoma, and nine of 33 (27%) kidney cancer patients.

However, people in the study with prostate and colon cancer were not helped by the drug.

About 14% of patients experienced serious side effects that often required hospitalization, and three patients (1%) died from inflammation of the lung. Brahmer says that the researchers are learning how to better identify and treat people at risk for serious side effects.

Moreover, "compared with chemotherapy, which is the mainstay for most of our patients, there were fewer side effects -- no hair loss, no serious nausea and vomiting, and they were not as prone to infections," Brahmer says. Other less severe side effects included fatigue, itching, and rash.

The PD-1 blocker also appears to have fewer side effects and greater anti-tumor activity than Yervoy, a different type of immune-system drug approved last year for the treatment of melanoma, says Antoni Ribas, MD. Ribas, a melanoma specialist at the University of California, Los Angeles, wrote an editorial accompanying the study in the New England Journal of Medicine.

The lung cancer results have doctors most -- albeit still cautiously -- enthused.

"This level of response in patients with advanced lung cancer, which is typically not responsive to immune-based therapies, was unexpected and notable," Brahmer says.

If the early results pan out, "this will be a game-changer for the treatment of lung cancer," says Louis Weiner, MD, director of Lombardi Comprehensive Cancer Center in Washington, D.C.

The study "really validates the importance of manipulating the immune response to eliminate cancer cells," he tells WebMD.

Although there have been some successes with immune-based therapies for melanoma and kidney cancer, this is the first time that lung cancer patients have been helped, says Weiner.

Immune Therapy Field Expanding

The anti-PD-L1 therapy was tested in about 200 patients. Tumors shrank in five of 49 (10%) non-small-cell lung cancer patients, nine of 52 (17%) melanoma patients, and two of 17 (12%) kidney cancer patients.

Nine percent of patients developed serious side effects, but none died from the treatment.

It's rare for such early-stage studies to be published in a major medical journal. Asked why she thought this research merited publication, Brahmer says, "Taken together, the studies show this pathway is important in cancer. We were able to block it in two different ways and get consistent results."

The researchers are now working to find molecular indicators that may help predict which patients are likely to be helped by the treatment and which will not.

Weiner says that the field of immunotherapy is expanding. Other companies are also developing PD-1 inhibitors. A number of companies are also working on cancer vaccines that retrain the immune system to attack tumors.

If the new drugs work and prove safe in later-stage studies, the hope is that combining them together, or with other anti-cancer agents, will further boost their effectiveness, Brahmer says.

SOURCES: 48th Annual Meeting of the American Society of Clinical Oncology, Chicago, June 1-5, 2012. Topalian, S. New England Journal of Medicine, published online June 2, 2012. Brahmer J. New England Journal of Medicine, published online, June 2, 2012. Ribas A. New England Journal of Medicine, published online, June 2, 2012. Julie Brahmer, MD, associate professor of oncology, Johns Hopkins Kimmel Cancer Center, Baltimore. Louis Weiner, MD, director, Lombardi Comprehensive Cancer Center, Washington, D.C.

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