Nonmelanoma skin cancers, such as basal cell carcinoma and squamous cell carcinoma, are very common, with more than 3.5 million cases diagnosed annually. In fact, it’s estimated that one in five Americans will develop skin cancer.
While melanoma tumors begin in the skin’s pigment-containing cells, basal cell carcinoma and squamous cell cancers develop in cells at the base of the outer layer of the skin. They rarely spread to other parts of the body, and therefore are much less likely than melanoma to be fatal, and they’re usually treated by simple surgical removal.
However, a rare condition called basal cell nevus syndrome is caused by an inherited mutation, and these patients, among other complications, develop very large numbers of invasive basal cell cancers beginning at a young age, says Thomas Kupper, MD, leader of the Center for Cutaneous Oncology at Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC).
Traditionally these patients needed many repeated surgeries to remove the cancers. New targeted drugs are now available that can shrink the tumors without surgery, but the cancers return when treatment is stopped.
Kupper is a specialist in research and treatment of cutaneous T cell lymphomas (CTCL). These are fairly rare non-Hodgkin lymphomas that develop not in native skin cells, but in immune T cells that have previously migrated to the skin, causing rashes, itchy plaques, and tumors. The most common type is called mycosis fungoides.
These cancerous T cells remain in the skin in about 70 percent of patients; in the other 30 percent, the cancer cells move into the lymph nodes and spread to other parts of the body. These patients require chemotherapy and often receive stem cell transplants.
The different types of CTCL cancers are treated with topical products, interferon, corticosteroids and monoclonal antibody drugs, depending on disease stage.
Kupper and Rachael Clark, MD, PhD, another researcher in the Center for Cutaneous Oncology, have determined that a monoclonal antibody drug, alemtuzumab or Campath, can be very effective in treating a rare type of CTCL called Sezary syndrome.
Gains in melanoma treatment
More than 73,000 new cases of invasive melanoma will be diagnosed in 2015, according to the American Academy of Dermatology. Melanoma can often be cured, but it’s an aggressive cancer that becomes life-threatening when it spreads.
Melanoma treatment has changed dramatically in the past five years, notes Andrew Werchniak, MD, clinical director of the Center for Cutaneous Oncology. For the 40 to 60 percent of melanomas that are driven by a mutant BRAF gene and protein, targeted BRAF inhibitor drugs are often effective, and are being used in combination with MEK inhibitors to combat drug resistance.
The best news in many years for metastatic melanoma patients is the development of new immunotherapy drugs. Some patients with advanced melanoma have had dramatic and long-lasting responses to drugs targeting proteins such as CTLA-4 and PD-1, which enable cancer cells to hide from the body’s immune system. These immunotherapy agents block the activity of these proteins, effectively taking the brakes off the immune system so its T cells can recognize and attack the melanoma throughout the body.
Last December, the Food and Drug Administration approved nivolumab (Opdivo), which targets PD-1, after it showed encouraging results in clinical trials. Research suggests that nivolumab may be even more effective when given along with another approved immunotherapy drug, ipilimumab (Yervoy), which blocks a different protein, CTLA-4. Another anti-PD-1 drug, pembrolizumab (Keytruda), was also approved in 2014 to treat patients originally treated with ipilimumab whose disease has progressed.
“With these new tools, there is a much higher chance of having a good outcome than five years ago,” says Werchniak. “But these tools are so new that we’re still trying to figure out how best to use them – in what sequence, and in what combinations, for individual patients.”