In a nutshell
The authors aimed to compare safety of a combination therapy over a single therapy in advanced melanoma patients.
Some background
In the advanced stage of 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 cell signalling and also in the function of another important protein called MEK. Drugs that stop the growth of cancerous cells with these mutations are known as BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi).
Vemurafenib (Zelboraf) and dabrafenib (Tafinlar) are BRAFi. Examples of MEKi are cobimetinib and trametinib (Mekinist). Previously, treatment with either BRAFi or MEKi was found to improve overall survival in advanced melanoma patients. However, these inhibitors frequently caused severe side effects in the skin.
Methods & findings
In this study, the safety of combination therapy of BRAFi and MEKi was investigated. Data from 44 patients with stage III/IV melanoma were reanalyzed. In all, 33 patients received either a BRAFi or a combination of BRAFi plus MEKi. Side effects analyzed included sensitivity to light, hair loss, rash and warts amongst others.
Those who received BRAFi alone had a cutaneous (skin-related) event-free period of 28 days on average. Those who received BRAFi and MEKi combination, the event-free period was 122.5 days.
The remaining 11 patients received both a BRAFi alone and a BRAFi plus MEKi combination at different times during their treatment. Of these, 10 patients (90.9%) developed severe cutaneous side events during BRAFi single therapy and 5 patients (45.5%) developed similar side effects during combination therapy.
The bottom line
The authors concluded that combination treatment with BRAFi and MEKi was associated with fewer cutaneous side effects and longer event-free period compared to treatment with a BRAFi alone.
The fine print
Data from a larger patient population would have helped understand the safety of the combination therapy better.
Published By :
Journal of the American Academy of Dermatology
Date :
Dec 01, 2014
