Recently developed treatment options offer hope for patients with melanoma, which is the most malignant form of skin cancer, with a 5-year survival rate under 20% for metastatic forms of the disease. Various factors contribute to an individual patient’s risk for developing skin cancer. An individual’s genetics, exposure to ultraviolet light, history of sunburn, and even their contact with certain chemicals or viruses could each contribute to the development of melanoma. It is possible for melanoma to develop in or near the site of a previous precursor lesion, or it could even develop in skin that appears healthy.
The annual incidence of melanoma has shown an increase over the decades. The American Cancer Society estimated that 9,940 deaths were caused by melanoma in 2015. If detected early, melanoma can be cured with surgical excision. If melanoma has progressed to an advanced state, treatment will typically expand to include pharmacotherapy. In recent years, the FDA has approved several new treatment options for patients with metastatic melanoma:
- Drugs targeting BRAF proteins: Zelboraf (vemurafenib) and Tafinlar (dabrafenib), indicated for the treatment of unresectable/metastatic melanoma with specific BRAF mutations.
- Drugs targeting MEK: Mekinist (trametinib), indicated for the treatment of unresectable/metastatic melanoma with specific BRAF mutations. Cotellic (cobimetinib), in combination with Zelboraf (vemurafenib), indicated for the treatment of unresectable/metastatic melanoma with specific BRAF mutations.
- Checkpoint inhibitors: Yervoy (ipilimumab), targets CTLA-4, indicated for unresectable/metastatic melanoma; it is also indicated for the adjuvant treatment of cutaneous melanoma. Keytruda (pembrolizumab), PD-1 inhibitor, indicated for treatment of patients with unresectable or metastatic melanoma. Opdivo (nivolumab), PD-1 inhibitor, indicated for unresectable/metastatic melanoma with specific BRAF mutations.
- Combinations: Cotellic (cobimetinib) plus Zelboraf (vemurafenib), indicated for the treatment of unresectable/metastatic melanoma with specific BRAF mutations. Opdivo (nivolumab) plus Yervoy (ipilimumab), indicated for unresectable/metastatic melanoma. Tafinlar (dabrafenib) plus Mekinist (trametinib), which targets BRAF and MEK respectively, for patients with unresectable/metastatic melanoma with specific BRAF mutations.
- Oncolytic virus therapy: Imlygic (talimogene laherparepvec), a genetically modified live oncolytic herpes virus therapy, used to treat melanoma lesions that cannot be removed completely by surgery.
As with many medications, there are reported side effects with these therapies, but though different, they are not typically worse than effects experienced by patients who receive chemotherapy or radiotherapy. Depending on the treatment, effects can include skin-related side effects, high fevers, diarrhea, joint pain, diarrhea, colitis, or serious immune-related reactions. Imlygic, the first FDA-approved oncolytic virus therapy, has been associated with fatigue, chills, fever, nausea, flu-like symptoms, and pain at the injection site, but herpes virus infection can also occur, since Imlygic is a modified live oncolytic herpes virus therapy. It is important for healthcare providers to instruct patients about possible side effects, what early signs to look for, and to report adverse reactions so treatment can be given.
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Salvatore Volpe, MD, FAAP, FACP, CHCQM
Chief Medical Officer