Skin reactions due to melanoma treatments

This review explored the skin toxicities associated with treatments for patients with metastatic melanoma caused by BRAF mutations.

Melanoma is a form of skin cancer that begins in the melanocytes, the cells that produce skin color. In metastatic melanoma, the cancer has spread to other areas of the body. Patients with metastatic melanoma typically do not respond well to chemotherapy treatments, therefore the development of therapies that target the genetic causes of metastatic melanoma have been an important advance. 70-80% of melanomas are caused by genetic mutations (defects) that lead to an uncontrolled increase in cell growth and spread. The BRAF mutation is responsible for approximately half of the melanomas found in younger patients, as well as melanomas not caused by sun exposure. BRAF inhibitors, such as sorafenib (Nexavar), vemurafenib (Zelboraf), and dabrafenib (Tafinlar), block the uncontrolled cell growth, and have been shown to increase both the time before the disease spreads (progression-free survival) and overall survival times. However, these treatments can cause multiple adverse effects, including many that involve skin toxicity, which can significantly lower a patient’s quality of life. The current review summarizes the skin toxicities associated with BRAF inhibitors.

BRAF inhibitors have been associated with many adverse events involving the skin, including increased itchiness and redness, alopecia (hair loss), and photosensitivity, in which even short periods of sun exposure can lead to painful blistering. Hyperkeratosis is a thickening of the skin, such as the formation of calluses. This reaction was found in 12% of patients treated with dabrafenib.

Multiple types of rashes have also been associated with BRAF inhibitors. These rashes generally begin 2 weeks after the start of treatment. Vemurafenib in particular has been associated with maculo-papular rash, which includes both flat red spots and raised bumps. Clinical trials involving this treatment have reported rashes in up to 45% of patients.

Squamous cell carcinoma (SCC) is a cancer of the upper layers of the skin. This, as well as a non-cancerous condition called keratoacanthoma that looks very similar to SCC, has been found in 6-7% of patients using sorafenib, and in 15-25% of patients treated with vemurafenib or dabrafenib. There are no reports of an SCC spreading to other areas of the body, or of it returning once removed. However, these effects highlight the need for close monitoring of patients using BRAF inhibitors. 

This review concluded that a number of adverse effects involving the skin can occur in patients using BRAF inhibitors. These effects can reduce the quality of life and should be closely monitored.

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