Side effects from combination of radiation and BRAF inhibitor therapy in melanoma

The authors analyzed the adverse effect of combination treatment with radiation and targeted therapy in melanoma. 

In advanced melanoma (stage III/IV), cancer spreads from the skin to other parts of the body. In the majority of advanced melanoma patients, BRAF genes are mutated (permanently changed). These genes are involved in cellular signaling and protein function. In BRAF mutated melanoma, these proteins remain permanently active. This results in the uncontrolled growth of cancer cells. BRAF inhibitors are drugs that stop certain cell signaling proteins used by mutated melanoma cells. Oftentimes, radiotherapy is needed along with BRAF inhibitors. Radiotherapy involves directing a beam of radiation at the tumor site to kill cancer cells. However, BRAF inhibitors such as vemurafenib (Zelboraf) and dabrafenib (Tafinlar) have been shown to make normal cells more sensitive to the harmful effect of radiation. This is called the radiosensitizing effect.

Further studies on the effect of BRAF inhibitors in radiotherapy sensitivity are needed. This will help to determine the appropriate treatment options for melanoma. 

The authors aimed to analyze the radiosensitizing effect of vemurafenib and dabrafenib in melanoma patients.

161 advanced melanoma patients were analyzed. 70 patients received radiotherapy in combination with BRAF inhibitors (group 1). 91 patients received radiotherapy only (group 2). The average follow-up time was 6.6 months.

The occurrence of acute radiodermatitis (skin disease associated with prolonged exposure to radiotherapy) was 36% in group 1. Following whole-brain radiotherapy, the occurrence of acute radiodermatitis was 44% in group 1. It was 8% in group 2. Overall, 40% of patients treated with vemurafenib experienced acute radiodermatitis. This was compared to 26% of patients treated with dabrafenib. Patients receiving vemurafenib as their BRAF inhibitor had increased radiosensitivity. Patients who switched from vemurafenib to dabrafenib also experienced increased radiosensitivity. Patients receiving dabrafenib only did not experience increased radiosensitivity. 

Follicular cyst proliferation (FCP – disease affecting the skin, hair and nails) occurred in 13% of all radiation treatments. Non-skin side effects included hearing disorders and difficulty swallowing. 

The authors concluded that melanoma patients could possibly be treated with radiation therapy in combination with BRAF inhibitors. They further suggested that patients treated with vemurafenib were more prone to side effects from radiation.  

If you are planning on combination therapy with radiotherapy and BRAF inhibitors, talk to your doctor about the benefits and risks of dabrafenib.