What types of skin-related side effects do biological treatments cause in patients with melanoma?

This article reviewed the types and frequency of different skin-related side effects that patients with melanoma experience while receiving biological treatments.

Treatment for patients with melanoma has changed in recent years from chemotherapy to biological therapies. Biological therapies include BRAF inhibitors and anti-PD-1 antibodies. BRAF inhibitors stop the growth of cancer in patients that have BRAF mutations (a type of genetic abnormality). Around 60% of patients with advanced melanoma have BRAF mutations. The most commonly used BRAF inhibitors are vemurafenib (Zelboraf) and dabrafenib (Tafinlar).  

Cancer often uses a molecule called PD-1 to switch off the immune system. Anti-PD-1 antibodies are a type of drug which blocks PD-1. This allows the immune system to be switched on and kill cancer cells.  The most commonly used anti-PD-1 drugs are nivolumab (Opdivo) and pembrolizumab (Keytruda). BRAF inhibitors and anti-PD-1 drugs have improved treatment results for patients but also cause more skin side effects. It is important to recognize the skin-related side effects of biological therapies for melanoma for better adherence to treatment.

Approximately 90% of patients receiving BRAF inhibitors develop side effects of the skin. 

Rashes are the most common type of skin side effect that patients experience. Up to 45% of patients develop rashes. Rashes most commonly develop on the face, scalp, and trunk. Squamoproliferative lesions (SPL) are a name for sores that can develop on patients’ skin. These are wart-like growths that are precancerous. 49 to 72.2% of patients receiving BRAF inhibitors develop these. 

Increased sensitivity to sunlight is also commonly caused by BRAF inhibitors.  30% of patients who receive vemurafenib and up to 3% of patients who receive dabrafenib develop sensitivity. This can range from mild to severe sensitivity. Between 20 to 56% of patients who receive BRAF inhibitors develop hair loss. 15 to 45% of patients develop reactions on their hands or feet such as numbness, blisters or rashes.  Some patients develop dermatitis, where the skin becomes itchy, dry or red and swollen.

Between 33% and 41% of patients receiving anti-PD-1 antibodies develop skin side effects.

Itchy skin (pruritus) develops in 13.2% of patients receiving nivolumab and 20.2% of patients receiving pembrolizumab. Depigmentation is the loss of skin color and occurs in patches. 7.5% of patients receiving nivolumab and 8.3% of patients receiving pembrolizumab develop depigmentation. Between 14.3% and 16.7% of patients receiving anti-PD-1 therapy develop rashes. Often these can be treated with creams.

Eczema, where patches of skin become itchy, red, cracked, and rough, occurs in 17 to 27% of patients.  Psoriasis is a condition where scaly patches are caused by excess skin. Anti-PD-1 treatment has been shown to cause psoriasis in some patients and worsen it in patients who already had it.

Bullous pemphigoid is where itchy blisters occur on patients’ trunks. It is increased in patients receiving anti-PD-1 treatment. Other skin side effects that some patients develop include increased sensitivity to sunlight, hair loss, and hives. Around 5.6% of patients develop acne during treatment.

The authors concluded that while biological treatments have improved results for patients, they have also increased skin side effects. The authors recommended consulting a dermatologist to help treat or prevent these side effects.