Risk of eye inflammation in advanced melanoma treated with vemurafenib

The authors assessed the risk of eye inflammation in late-stage melanoma patients treated with vemurafenib (Zelboraf).

In advanced melanoma (stage 3/4), cancer spreads from the skin to other parts of the body. BRAF genes are often mutated (permanently changed) in advanced melanoma. BRAF inhibitors (BRAFi) such as vemurafenib stop (inhibit) certain cell signaling proteins in melanoma cells containing mutated BRAF genes. Although vemurafenib has shown improved survival of advanced melanoma patients, it can cause side effects such as uveitis. Uveitis is the inflammation of the eye involving three parts of an eye (iris, ciliary body or choroid)-together known as uvea.

A detailed study evaluating the risk of uveitis from vemurafenib treatment in melanoma patients would be beneficial. 

The authors aimed to assess the occurrence and severity of uveitis in melanoma patients treated with vemurafenib.

In this observational study, 78 vemurafenib-treated patients were included. Out of these, 7 patients were diagnosed with uveitis.

The average age of patients having uveitis was 74.7 years. The initial vemurafenib dose was 960 mg twice per day in 6 patients and  480 mg twice per day in 1 patient. The average time from the treatment until the start of eye inflammation was 5.6 months. The inflammation was generally mild. 1 patient, however, had severe inflammation complicated by retinal (critical layer of tissue at the back of the eye) detachment and vision loss. 1 out of 7 patients had water retention in eye. 

Overall, 5 patients discontinued treatment. Improvement of symptoms was observed in these patients when treatment was stopped. 2 patients had reduction of symptoms in spite of continued treatment. After discontinuation, 4 patients restarted on vemurafenib treatment. 2 out of these 4 patients had return of uveitis symptoms. 

The authors concluded that uveitis could be an important side effect of vemurafenib in melanoma. However, benefits from vemurafenib were found to be greater than the risk to patients’ vision. 

A larger patient population is needed for the results from this observational study to be widely applied.