Can a combination of dabrafenib and trametinib improve relapse-free survival after removal of stage 3 melanoma?

This study investigated the long-term effectiveness and risks of the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) for patients with stage 3 melanoma after tumor removal.

It showed that the combination of the two drugs can increase survival without return or spreading of cancer.

Melanoma is an aggressive type of skin cancer. It has a high tendency to spread to other parts of the body (metastasis). In stage 3 melanoma, cancer has spread to nearby lymph nodes. After successful initial therapy such as chemotherapy or radiation, cancer can be removed. Afterward, additional treatment is necessary to avoid the return (relapse) or further metastasis. 

Previous research over the period of one year has shown that the drug combination dabrafenib and trametinib can help lower the chance of return of metastasis of cancer. These are targeted therapy drugs. They target certain proteins on cancer cells and stop their growth and spread. The risks and effectiveness of the combination of dabrafenib and trametinib over a longer period of time were unknown.

For this study, 870 patients with a gene mutation (abnormality) such as BRAF V600E or V600K were included. All of the patients had stage 3 melanoma that was already treated and removed by surgery. Patients were randomly assigned to receive either daily 300 mg of dabrafenib and 2mg of trametinib or two identical placebos. The average follow-up period was 58-60 months.

After 5 years, 36% of the placebo-group survived without relapse compared to 52% of the patients who received the drug combination. The risk of cancer relapse or mortality was 49% lower with trametinib and dabrafenib compared to placebo.  

The percentage of patients alive without metastasis was 54% in the placebo group and 65% in the dabrafenib plus trametinib group. This risk of developing metastasis was 45% lower with the drug combination compared to placebo.

There were no significant differences in the occurrence and severity of side effects between the two groups.

The study suggests that the combination of dabrafenib and trametinib can improve survival without relapse or metastasis in patients with stage 3 melanoma after tumor removal.

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