New drugs stir hope on melanoma

 Dr. Keith T. Flaherty leads a new study on melanoma.
Dr. Keith T. Flaherty leads a new study on melanoma.

After a decade of stalled progress, a flurry of new studies is sparking hope in the fight against the deadly skin cancer melanoma.

The studies, which show promising results from experimental drugs, are being presented at the annual meeting of the American Society of Clinical Oncology in Chicago, which concludes Tuesday.

“The field for melanoma is changing so incredibly rapidly, it’s hard to even keep up with for us,” said Dr. F. Stephen Hodi, director of the melanoma center at Dana-Farber Cancer Institute in Boston. “Really, it’s the golden age of therapeutics right now.”


In a study published online Monday in the New England Journal of Medicine, 322 patients with metastatic melanoma and a specific genetic mutation in their tumors were randomly assigned to receive either a GlaxoSmithKline experimental drug called trametinib or chemotherapy. On average, the drug prevented tumor growth for 4.8 months — more than three months longer than the group receiving just conventional chemotherapy.

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Other attempts to target melanoma driven by the same gene mutation, including a drug approved last year, have had remarkable success. But almost invariably, the cancer returned as tumors developed resistance to the therapy. Now, there is increasing hope that new drugs like trametinib might offer another option, or work in combination with other drugs.

“It continues to be too good to be true,” said Dr. Keith T. Flaherty, director of developmental therapeutics at Massachusetts General Hospital and leader of the study.

“To be able to quickly have a rational basis for being able to multiply the effects [of existing therapies]; it’s like a second leapfrog moment, very quickly following the first.”

Dr. Michael A. Davies, assistant professor in melanoma medical oncology at the University of Texas MD Anderson Cancer Center, said that although the drug controlled the cancer for a limited period of time, it represents an important weapon to add to the arsenal.


“We went from 1999 all the way to 2010 without any new treatments for metastatic melanoma,” Davies said. “This represents our third agent in a randomized trial to show a significant improvement” in tumor control and overall survival.

Much of the excitement about drugs like trametinib, which inhibit proteins called MEK1 and MEK2 that are activated in tumor cells, stems from the possibility of using them in combination.

Last year, two major new drugs for melanoma were approved: Genentech’s vemurafenib, targeted at genetic mutations that underlie half of melanoma cases, and Bristol-Myers Squibb’s ipilimumab, which activates the immune system. Although each one showed the promise of a different approach to treating the cancer, both also had limitations.

Genentech is enrolling patients in a trial of the combination of vemurafenib and its own experimental MEK inhibitor.

At the cancer meeting, the results of an early trial of a separate combination therapy using trametinib and an experimental drug that targets the BRAF mutation, is also scheduled to be presented. In that trial, tumor growth was halted for an average of 7.4 months among 77 patients who had not previously received a targeted therapy.


Clinicians hope the combination can delay the development of resistance, and said the strategy is also exciting because in tandem, the drugs may have fewer side effects.

‘This represents our third agent in a randomized trial to show a significant improvement’ in tumor control.’

Aside from approaches that target specific genetic changes, there is also increasing excitement about therapies that help enable the immune system to attack a tumor. Among the most anticipated results presented at the conference are those describing an investigational therapy made by Bristol-Myers Squibb, which has been tested in a large, but early stage trial, showing promising effects in lung, skin, and kidney cancers.

Dr. David McDermott, director of the biologic therapy program at Beth Israel Deaconess Medical Center, said that nearly 30 percent of patients with kidney cancer or melanoma responded to the treatments, and five companies are working on such drugs.

McDermott said that although much work remains to be done — the drug still needs to be more carefully tested in randomized, large trials — researchers have seen tantalizing evidence that it may have long-lasting effects. A spokeswoman for Bristol-Myers Squibb said the company expects trials for non-small cell lung cancer and kidney cancer to be launched this year, and a melanoma trial by early 2013.

In the subset of almost 100 melanoma patients treated with the experimental drug, Dana-Farber’s Hodi said there have been patients whose disease has stabilized, with responses lasting not just weeks, but a year or more.

Carolyn Y. Johnson can be reached at Follow her on Twitter @carolynyjohnson.