Combination therapy is more effective in treating metastatic melanoma

The authors aimed to determine the effects of combination therapy compared to single therapy in melanoma patients with BRAF mutations.

Melanoma can arise as a result of family genetics where mutations in specific genes such as BRAF genes (controls the functions needed for cell growth) can be passed on to family members. Patients with BRAF mutations are usually treated with vemurafenib (Zelboraf) or dabrafenib (Tafinlar) which are the most common single therapies used, as these drugs are effective in preventing BRAF functioning within cancer cells.

In some patients resistance to BRAF treatments can occur, rendering the drug ineffective. Other treatment options available for melanoma include trametinib (Mekinist – targets and stops proteins overactive in melanoma) which can be used alone or in combination with dabrafenib to treat BRAF mutated melanoma.

The authors aimed to compare the benefits of combination treatment and single treatment in melanoma patients with BRAF mutations.

704 patients were used in this study. The follow-up time was between 10-11 months.

Patients were separated evenly into two groups: 352 patients underwent combination-treatment which involved treatment with dabrafenib and trametinib and 352 patients underwent single-treatment which involved treatment with vemurafenib.

The average overall survival rate (percentage of patients who are still alive following diagnosis or treatment)  for single treatment at 12 months was 65%  compared to 72% in combination treatment. The average progression-free survival (time from treatment until cancer progresses) was 7.3 months with single treatment and 11.2 months with combination treatment. The response rate (patients whose cancer shrank or disappeared after treatment) for single treatment was 51%, lasting an average of 7.5 months, compared to 64%, lasting an average of 13.8 months for combination treatment.

Complete response (signs of cancer disappear in response to treatment) occurred in 8% of patients after single treatment compared to 13% of patients after combination treatment. After treatment was completed 43% of single treatment patients required additional treatment compared to 20% of combination patients.

Severe adverse events (life-threatening or disabling side-effects of treatment) occurred in 63% of single treatment patients compared to 52% of combination treatment patients. In the single therapy group the most common side effects were joint pain (51%), rash (43%), hair loss (39%), diarrhea (38%), nausea (36%) and fatigue (33%).In the combination therapy group the most common side effects were joint pan (53%), nausea (35%), diarrhea (32%), chills (31%), fatigue (29%), headache (29%) and vomiting (29%). 

The authors conclude that dabrafenib and trametinib treatment significantly improved overall survival compared to vemurafenib alone in patients with BRAF mutations.

The duration of vemurafenib was 4 months shorter than combination treatment and may have biased the results. Dabrafenib and trametinib were developed by GlaxoSmithKline, who sponsored the study. 

If you are considering dabrafenib, trametinib or vemurafenib as single or combination treatment options please discuss potential side-effects with your doctor.