Phase III clinical trial for Trametinib shows improved survival in metastatic melanoma patients with BRAF mutations

This study presents the results of a phase III clinical trial evaluating the efficacy and safety of the drug trametinib for the treatment of metastatic melanoma patients with BRAF mutations.

BRAF is a protein from a chain of proteins in the cell called the MAP kinase pathway. These play a role in cell division and growth. About 50% of melanomas arise because of a genetic defect in the MAP kinase pathway which causes the BRAF protein to malfunction (BRAF mutation). As a result, the pigmented cells of the skin (melanocytes) start multiplying and growing abnormally, forming a melanoma. Metastatic melanoma means that the cancer has spread to distant lymph nodes or organs of the body such as the liver, lungs or brain. In metastatic melanoma patients with BRAF mutations, the cancer actually becomes addicted to this protein. Therefore, it can be treated with drugs that block this specific protein (targeted therapies). As a result, targeted therapies can help stop the cancer's growth, relieve symptoms and prolong survival for patients with metastatic disease. Trametinib is an experimental drug that blocks the MAP kinase pathway and shows good results in clinical trials for metastatic melanoma patients with BRAF mutations.

This clinical trial included 322 metastatic melanoma patients with BRAF mutations. Patients received either trametinib once daily, or chemotherapy consisting of dacarbazine or paclitaxel every three weeks. Parameters measured in the study were progression-free survival, or PFS (defined as the period of time without cancer progression), overall survival and treatment-related side effects.

Patients who received trametinib had a 55% higher PFS compared to patients who received chemotherapy (4.8 months versus 1.5 months). After 6 months of follow up, the overall survival was 81% in the trametinib group and 67% in the chemotherapy group. The most common side effects for trametinib were skin rashes, diarrhea and swelling of the feet.

In conclusion, in comparison to chemotherapy, trametinib significantly improved progression-free survival and overall survival among patients who had metastatic melanoma with BRAF mutations.

Despite these promising results from clinical trials, trametinib is not yet approved by the FDA for the treatment of metastatic melanoma patients. Further studies are needed to determine the role of trametinib in the treatment of melanoma patients. 

This study was funded by GlaxoSmithKline Pharmaceuticals, the manufacturer of trametinib.