Effectiveness of combination therapy on quality of life in advanced BRAF-mutant melanoma

The authors evaluated the effectiveness of combination therapy with dabrafenib (Tafinlar) and trametinib (Mekinist) on health-related quality of life in advanced melanoma patients. The authors found out that the combination therapy prolonged survival and decreased treatment-related adverse events. 

In advanced melanoma (stage 3 or 4), cancer spreads from the skin to other parts of the body. Targeted therapy has shown improved outcomes in these stages of the disease. Targeted therapies block specific genes, such as BRAF, that are often mutated in melanoma patients.

BRAF inhibitors such as dabrafenib and vemurafenib (Zelboraf) block certain proteins in BRAF-mutated melanoma cells. BRAF inhibitors have led to significant improvements in the treatment of melanoma. However, patients can become resistant to BRAF inhibitors. It is thought that a combination of therapies that inhibit different proteins may be more effective than one inhibitor alone. Trametinib, for example, blocks a different protein than dabrafenib. These treatments may be more effective when used together. The effect of combination therapy with these inhibitors on quality of life needs to be further evaluated.

The authors aimed to compare the effectiveness of combination therapy with dabrafenib and trametinib to that of vemurafenib alone in advanced melanoma.

704 patients were included in this phase III trial. All patients had advanced melanoma that could not be surgically removed. 352 patients in group 1 received a combination of dabrafenib and trametinib. 352 patients in group 2 received vemurafenib. The average follow-up time was 11 months in group 1 and 10 months in group 2. The effect of treatment on quality of life and medical symptoms were evaluated based on a questionnaire. Progression of disease was also measured. The questionnaires were answered every 8 weeks starting from week 8 to week 48.

Quality of life was scored higher in group 1 compared to group 2 in all areas, such as social functioning, physical functioning and emotional functioning. These results were similar in patients following disease progression as well.

Symptoms such as pain, diarrhea, nausea and vomiting, tiredness, and sleeplessness, among others, were also recorded. Symptoms were lower in group 1 compared to group 2. Fever was reported more often in group 1 than in group 2. These results were similar following disease progression.

The authors concluded that combination therapy with dabrafenib and trametinib was beneficial to patients over single therapy with vemurafenib.

This study was funded by GlaxoSmithKline, the manufacturers of dabrafenib and trametinib.