In 2016, in the U.S., approximately 76,380 new melanomas will be diagnosed, and about 10,130 people will die from this disease. That is more than one life claimed every hour in the U.S. Moreover, the incidence of melanoma is on the rise in the U.S. and around the globe.
The main risk factor for melanoma, as for all skin cancer, is exposure to natural and artificial ultraviolet (UV) light. According to the American Academy of Dermatology, more people develop skin cancer from tanning than develop lung cancer from smoking.
Although melanoma is often easier to detect in its earlier stages than most cancers, it is also more likely to spread (metastasize) to other parts of the body. Metastasis represents the most significant cause of death from the disease. The 5-year survival rate for localized (stage I and II) melanoma is 98%; however, this drops to 17% in cases where cancer has metastasized to distant sites or organs. (These numbers are based on historical data collected up to 2011, and may change as immunotherapy is more widely used.)
Treatment for melanoma depends on the properties of the tumor and the stage at which the cancer is detected. If discovered early, the tumor may be removed surgically. In the case of advanced disease, the tumor is removed along with surrounding normal tissue and a sentinel lymph node. If a biopsy reveals that the cancer has spread to lymph nodes, treatments may include more extensive surgery, immunotherapy, targeted therapy, or clinical trial participation. Radiation therapy is sometimes used as well, depending upon properties of the tissue removed at surgery.
Since 2011, eight new drugs have been FDA approved for the treatment of melanoma, including four immunotherapies and four targeted therapies. The immunotherapy drugs are ipilimumab (Yervoy®), pembrolizumab (Keytruda®), nivolumab (Opdivo®), and talimogene laherparepvec (T-VEC, Imlygic™). The first three drugs are checkpoint inhibitors that “take the brakes off” the immune system and enable it to fight cancer; the last is an oncolytic virus therapy that stimulates stronger anti-tumor immune responses.
The targeted therapies are vemurafenib (Zelboraf®), dabrafenib (Tafinlar®), trametinib (Mekinist®), and cobimetinib (Cotellic®). These drugs target common genetic mutations, such as the BRAFV600 mutation, found in a subset of melanoma patients. Three interferon and interleukin-based treatments—aldesleukin (proleukin®), interferon alfa-2b (INTRON®), and pegintereferon alfa-2b (Sylvatron®)—are also approved for melanoma patients.
Despite the recent FDA approvals of these drugs, some patients with advanced metastatic melanoma still have a significant risk of mortality. A substantial unmet need remains for new successful therapies in patients with this disease.
The side effects of immunotherapy are different than chemotherapy. Whereas chemotherapy’s side effects—nausea, hair loss, vomiting—stem from its destruction of all rapidly-dividing cells, both healthy and cancerous alike, immunotherapy’s side effects are often immune-related, and commonly include inflammatory symptoms such as rash, diarrhea, pruritus, and colitis, amongst others. These immune-related adverse events can be quite serious and even fatal, but are typically reversible when effective treatment guidelines on side effect management are followed.