Managing BRAF Inhibitor Associated Skin Toxicity

Mario E. Lacouture, MD, a dermatologist at Memorial Sloan-Kettering Cancer Center, describes the management of dermatologic adverse events (AEs) that occur as a result of treatment with BRAF inhibitors, such as vemurafenib and dabrafenib.

On average, 90% of patients treated with a BRAF inhibitor will develop dermatologic AEs, especially with vemurafenib, Lacouture notes. These AEs consist primarily of a maculopapular rash (60%) and photosensitivity (50%), as well as hair thinning, hand-foot skin reaction, and hyperkeratosis (10%).

In general, since it’s a maculopapular rash, it can be treated with topical or oral corticosteroids. If needed, a dose interruption generally resolves the rash. Following treatment interruptions, if the rash returns, it is less sensitive. Oftentimes, after this treatment holiday, the rash does not come back at all, Lacouture states.

Photosensitivity appears to develop exclusively in patients receiving the BRAF inhibitor vemurafenib, Lacouture says. As a result of this sensitivity, sunburn may occur after only 10 minutes of exposure. As a result, broad-spectrum sunscreen containing UVA and UVB protectants should be applied at least every two hours. These sunscreens should contain a sun protection factor of at least 30. Sunscreen should be applied in an adequate amount, since inadequate application quantity is a commonly made mistake. At every application of the entire body, patients should apply an amount that is equal to about an ounce or roughly the size of a golf ball, Lacouture states.

In addition to sunscreen, Lacouture recommends wearing a broad brimmed hat and sun protective UVA/UVB sunglasses, since photosensitivity may also occur in the ocular conjunctiva.

Both vemurafenib and dabrafenib are associated with hand-foot skin reaction in approximately 10% to 20% of patients, Lacouture states. This reaction usually consists of a hyperkeratosis or thickening of the skin in the palms and soles. These reactions are usually treated with topical agents 2 to 3 times a day. These treatments include exfoliants and agents that contain ammonium lactate, salicylic acid, or urea at high concentrations of up to 40%, Lacouture suggests.