Melanoma: Ready for Takeoff

New therapies are enhancing melanoma treatment.

For several years, Bobby Harsh had strived to stay one step ahead of melanoma, as the aggressive form of skin cancer moved from a lesion on his left cheek in late 2007 to later gaining a foothold in his lungs.

The 40-year-old Maryland state trooper had extensive surgery, involving some 90 stitches that traced a horseshoe shape on the left side of his face. The melanoma, 4 millimeters in depth, was classified as stage 2C. Despite no indication that it had reached his lymph nodes, Harsh adopted an aggressive approach, enrolling in a clinical trial testing a vaccine treatment.

While he waited to qualify—all medication had to leave his system first—he decided to go ahead with a long-planned trip, visiting the national parks in a recreational vehicle with his wife and three teenage children. "I guess I would say that I'm a realist," he says, describing his mindset then. "We knew that the prognosis was very, very poor. At that point in time, you're looking for miracle kind of things."Harsh’s “miracle” arrived in the form of a drug called Yervoy (ipilimumab), a new intravenous agent that’s designed to harness the body’s immune system to better attack the cancer. He started treatments in September 2009. Fewer than three months later, the first set of scans showed evidence of the tumors’ shrinkage.

Yervoy, which was approved by the Food and Drug Administration in March, is among the first of several long-awaited drug treatments for advanced melanoma. Melanoma, the virulent cousin of more common skin cancers like basal cell carcinoma and squamous cell carcinoma, has been traditionally difficult to eradicate once it migrates beyond the skin’s surface. Other drugs now in research development are also showing promise, building on insights into mutations of specific genes, such as BRAF and c-kit, which might influence melanoma’s growth.

Overall the five-year survival rate for melanoma—diagnosed in 68,000 people in 2010—is quite high compared with many other malignancies, 91.4 percent according to National Cancer Institute data. But it drops to 62 percent once the cancer infiltrates the lymph nodes and much further, to 16 percent, if it spreads elsewhere in the body.

Moreover, melanoma has an extraordinary capacity for dormancy, says John Kirkwood, MD, director of the melanoma and skin cancer program at the University of Pittsburgh Cancer Institute. Following surgery, scattered cells that aren’t detectable by imaging scans can lurk and perhaps won’t pose a problem for years. Kirkwood described a patient he’d seen the prior day who was treated for stage 1 melanoma two decades before. Melanoma had just emerged in a nearby lymph node that appeared to stem from the initial tumor. “Only now, like Rumpelstiltskin, it has awakened to do its havoc,” Kirkwood says.

The recent treatment advances, although exciting, don’t extend to everyone. About 30 percent of patients had some degree of response to Yervoy, according to results published last year in The New England Journal of Medicine. Vemurafenib (also called PLX4032), which targets a BRAF gene mutation, has been able to shrink tumors in a higher percentage of patients but only transiently.

Still, they show promise as another treatment tool, along with more traditional approaches like surgery and chemotherapy. In fact, there’s an alphabet soup of drug combinations, both announced and in the works, that researchers and patient advocates hope will boost survival in patients who can’t be cured by surgery alone. The challenge is how to effectively and efficiently identify the optimal treatment combinations, says Timothy Turnham, PhD, executive director of the Melanoma Research Foundation.

“We are in a strange situation where we have very few approved drugs that are effective in metastatic melanoma,” he says. “But we have a lot of drugs in the pipeline that probably will be effective if used in the right way.”

Melanoma is so named because it develops in the pigment-carrying cells called melanocytes. By far the most lethal skin cancer, with about 8,700 deaths in 2010, it’s also becoming more common. Diagnoses among whites have jumped by more than 60 percent during the past 30 years, according to the National Cancer Institute. The largest driver is excessive exposure to ultraviolet radiation, primarily from the sun and tanning beds. But other risk factors can be influential, including family history of melanoma and a past history of basal cell or squamous cell cancers. Malignancy also is far more common in whites than in other racial or ethnic groups.

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