New Lung Cancer, Melanoma Drugs Create Stir

June 6, 2010— -- Two novel anti-cancer therapies -- one that targets a type of lung cancer, the other a drug that trains the body's immune system to fight off melanoma -- created a stir at a major cancer meeting this weekend.

Both therapies are still in their experimental phases; however, physicians at the American Society of Clinical Oncology's annual conference in Chicago were hopeful that the different approaches could change the way doctors treat cancer.

Targeted Therapy Shows Promise Against Lung Cancer

One of these, a novel targeted therapy presented at the meeting on Sunday for non-small cell lung cancer, has yet to pass many clinical hurdles; still, the drug, known as crizotinib, has demonstrated the ability to shrink tumors in about 90 percent of patients with advanced disease, according to Dr. Yung-Jue Bang of Seoul National University in South Korea, one of the leaders of the study.

The drug targets a protein in the body -- dubbed EML4-ALK -- which is responsible for tumor growth in up to 5 percent of all patients with non-small cell lung cancer. Interestingly, while most people with non-small cell lung cancer are smokers or former smokers, the protein in question is most often found in people who have never smoked. Indeed, in the study, Bang said, most patients were only former smoker or had never smoked at all.

It's a "very important story," said Dr. Mark Kris of Memorial Sloan-Kettering Cancer Center in New York City, who was not part of the study but moderated the press conference at which some of the data were presented.

For one thing, he said, the study demonstrates the speed with which discoveries can be translated to clinical testing. The protein that the therapy targets was first reported in 2007, and that finding is now starting to show results in clinical trials.

"In just three short years we've gone from a description of [a cancer gene] to a therapy," he said.

He also said that patients with the mutation that leads to the protein "can expect a dramatic benefit."

Indeed, in the study of 82 patients with advanced disease, Bang and colleagues found that the patients had a 72 percent probability of halting the progress of cancer at six months after starting the therapy. The majority of these patients saw their tumors shrink by more than 30 percent, he said, and some saw their cancers disappear.

Melanoma Therapy Turns Immune System Against Cancer

Likewise, researchers behind a promising study on the immune-stimulating agent ipilimumab reported the first-ever overall survival benefit with any treatment in a clinical trial involving the skin cancer known as metastatic melanoma.

In the study, led by Dr. F. Stephen Hodi of the Dana-Farber Cancer Institute in Boston, the experimental antibody treatment extended median survival to 10.1 months in patients with refractory malignant melanoma, compared with 6.4 months for patients treated with a different therapeutic vaccine -- a 34 percent reduction in the risk of death.

Malignant melanoma is notoriously difficult to treat; existing anti-cancer vaccines tended to improve the cases of a mere 5 to 10 percent of patients, said Dr. Petra Rietschel, director of melanoma and sarcoma medical oncology at Montefiore-Einstein Center for Cancer Care in New York City.

Nothing else has been very effective either in the metastatic melanoma setting, the researchers said, noting that enrollment in a clinical trial for an experimental treatment is considered the standard of care once chemotherapy or other commonly used treatments fail.

"Melanoma is one of the cancers that is relatively chemoresistant and does not have any options so far," Rietschel said.

However, Rietschel warned, the targeted agent isn't without its side effects.

"You have to be very careful with this and pay attention to stop it in time," Rietschel said.

Immune-related adverse events were most common with the drug, and seven of the 14 deaths in the study were associated with immune-related adverse events.

Novel Melanoma Therapy: When Will It Be Widely Available?

"Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment," Hodi's group wrote in the New England Journal of Medicine, where the results were published.

Ipilimumab works by removing the "brakes" on the immune system's attack on melanoma by blocking a specific molecule that acts as a checkpoint in the body's destruction of cancer cells.

Hodi's trial involved 676 patients with stage III or IV melanoma that could not be removed through surgery. The researchers reported that ipilimumab reduced risk of progression of the disease, and it also appeared to improve survival rates in the patients taking the drug.

These data will likely be enough to approach the U.S. Food and Drug Administration for an indication in refractory metastatic melanoma, study coauthor Dr. Jedd Wolchok of Memorial Sloan-Kettering Cancer Center in New York City said in an interview.

"If [ipilimumab] gets approved, I think it will be used for the majority of people with metastatic melanoma in the United States," he said.