Effect of combination therapy in advanced melanoma with BRAF mutation

The authors evaluated the effectiveness of combination therapy in advanced melanoma patients with mutated (permanent changes) BRAF genes.

In advanced melanoma (stage III/ IV), cancer spreads from the skin to other parts of the body. Targeted therapy has been shown to improve patient outcomes in the advanced stages of melanoma. Targeted therapy attacks specific genes such as BRAF. These genes are often mutated in melanoma patients. BRAF inhibitors such as dabrafenib (Tafinlar) can be used as a targeted therapy to stop certain cell signaling proteins (e.g. MAPK and MEK) used by BRAF mutated cancer cells. However, some patients may develop a resistance to BRAF inhibitors which can lead to secondary cancer growth. The combination of BRAF and MEK inhibitors (for example trametinib [Mekinist]) has been shown to delay the development of resistance. 

The effect of combination therapy with BRAF and MEK inhibitors needs to be further evaluated for treatment in advanced melanoma.  

The authors aimed to compare the effectiveness of combination therapy with BRAF and MEK inhibitors to that of BRAF alone in advanced melanoma.

423 patients were included in this phase III trial. All patients had advanced melanoma that could not be surgically removed. None of the patients had received any previous treatment. Patients in group 1 received a combination of dabrafenib and trametinib. Patients in group 2 received dabrafenib and a placebo (control drug used instead of the active drug). The median (midpoint) follow-up time was 9 months.

The median progression-free survival (time following treatment before the disease progressed) in group 1 was 9.3 months. It was 8.8 months in group 2. Overall, there was a 25% reduced risk of disease progression or death in group 1 compared to group 2. The overall response (partial or complete disappearance of tumor) was 67% in group 1. It was 51% in group 2. At 6 months, 93% of patients in group 1 and 85% of patients in group 2 were still alive following treatment.

2% of patients in group 1 and 9% of patients in group 2 developed secondary cancer. 51% of patients in group 1 developed a fever. This was compared to 28% in group 2. Severe or life threatening fevers were more common in group 1 compared to group 2. 

The authors concluded that combination treatment with dabrafenib and trametinib improved progression-free survival in advanced melanoma compared to treatment with dabrafenib alone. 

If you have BRAF mutated melanoma, please talk to your doctor about dabrafenib–trametinib combination therapy.