New Treatments for Melanoma
New Treatments for Melanoma | Melanoma, Metastatic Melanoma, Skin Cancer, Sunscreen, Vemurafenib, Ipilimumab, Dr. Jeffrey Sosman, Vanderbilt-Ingram Cancer Center

(L-R) Dr. Jeff Sosman, patients Charles Mason and Roger Johnson, and Dr. Igor Puzanov are all smiles at a VICC event. Both patients have been on vemurafenib for two years and are still doing well. Photo courtesy of Anne Washburn.
Winter had its chance. Now it’s time for crystal blue skies and lots of sunshine spreading warmth over Middle Tennessee.

The Nashville area offers many outdoor activities that combine great opportunities for exercise with a good dose of vitamin D. However, while your patients would never dream of hiking through Edwin Warner Park in bare feet, too often they think nothing of spending hours outdoors without appropriately covering their bare skin.

Jeffrey A. Sosman, MD, a professor of Medicine at Vanderbilt-Ingram Cancer Center and the director of the Melanoma & Tumor Immunotherapy Program, said primary prevention through sun smart protection is still the very best option to keep from developing melanoma.

“We tend not to use heavy enough sunscreen. If it’s going to be used, it needs to be used correctly and that involves using a lot of it,” Sosman stressed. He also noted no sunscreen is actually waterproof so it must be reapplied often.

The medical oncologist, who was recently named to the national melanoma research ‘Dream Team,’ said that if primary prevention fails, then the next best option is to catch melanoma early. “Melanoma tends to generally be curable in its early stages, if diagnosed and biopsied when it hasn’t penetrated deep into the skin,” he said. “However, when it does penetrate deep or spread through the lymph nodes or spread throughout the body, it’s very difficult to treat and generally is not curable at all.”

Up until recently, he continued, there were only two FDA-approved treatments for advanced melanoma. Now, however, the science is rapidly expanding.

After a draught of 14 years, two new drugs were approved in 2011 to treat metastatic melanoma. Both have shown they extend the survival rate of patients with the advanced form of the disease, which wasn’t true of the two older drugs.

In fact, investigators at VICC and 12 other centers in the U.S. and Australia have recently released results from a Phase 2 clinical trial co-led by Sosman that found vemurafenib (available commercially as Zelboraf®) nearly doubled the median survival time in the majority of patients. In the trial, the median overall survival was nearly 16 months as compared to the typical survival of six to 10 months for most patients with advanced melanoma.

The drug only works in patients with a BRAF V600 mutation in their tumor, which occurs in nearly half of all metastatic melanomas. “We now have a drug that can very specifically block that genetic mutation,” said Sosman.

A total of 132 patients with stage IV, BRAF-positive melanoma were enrolled in the Phase 2 trial. All of the patients had received at least one form of systemic treatment before enrollment. From the group, 47 percent had a partial response to the drug and 6 percent exhibited a complete response, for an overall response rate of 53 percent.

Unfortunately, Sosman noted, almost all patients ultimately become resistant to vemurafenib and do relapse. However, a study published last month out of UCLA’s Jonsson Comprehensive Cancer Center might have hit upon one of the reasons for resistance.

The UCLA scientists found that in some patients the mutated BRAF gene driving the cancer amplified in the face of the inhibitor. By increasing the copies of the mutated BRAF gene, the cancer tried to overproduce the drug target. Put simply, the melanoma replenishes its army of mutated BRAF genes until the inhibitor is effectively outnumbered. Since the FDA-approved dose is already at the maximum level of tolerance, it isn’t as simple as increasing the amount of vemurafenib given. Still, the insight into the resistance mechanism could help researchers find other options to thwart the replication of the mutated BRAF gene.

The second drug, ipilimumab, is not BRAF-specific. “This is a drug that works through the immune system,” explained Sosman. “Basically, it’s an antibody that binds to your immune cells. It takes the brakes off the T-cell and allows those cells to do the job of attacking the cancer.”

However, this drug is effective in a much smaller number of melanoma patients and can take months to actually begin working. “So it’s not a very effective treatment in someone who is symptomatic and needs a quick response,” noted Sosman. Still, he continued, “If you’re in that minority of patients who benefits, then you may have a very long benefit.” Sosman has patients who remain alive two and three years out on ipilimumab.

One exciting line of future research, he continued, is to combine the two new drugs to see if it’s possible to take advantage of the features of both to extend survivability and bring new hope to patients with this deadly form of cancer.