Long-term outcomes with dabrafenib combined with trametinib in metastatic melanoma

This study investigated the long-term safety and effectiveness of dabrafenib (Tafinlar) and trametinib (Mekinist) in metastatic melanoma. Researchers suggested that this treatment increased overall survival in melanoma patients.

Some melanoma patients have a mutation (permanent change) in the BRAF gene. Dabrafenib (BRAF inhibitor) is used to treat these tumors. However, over time patients can become resistant to the treatment. This resistance happens due to the reactivation of a certain protein (called MAPK) that allows for tumor growth. Therefore, adding trametinib (MAPK inhibitor) to the treatment can overcome BRAF resistance. The long-term outcomes of this treatment in patients with metastatic (spread disease) BRAF-mutated melanoma are not clear. 

This study reported the long-term safety and effectiveness of the treatment with dabrafenib and trametinib in BRAF-mutated melanoma. 162 patients were randomly assigned to receive dabrafenib only (54; group 1) or dabrafenib combined with 2 mg trametinib (54; group 2). (A separate group of 54 patients was treated with dabrafenib combined with 1 mg trametinib.) Patients were followed for up to 5 years.

Over the course of the study, 45 patients from group 1 had joined group 2 after disease progression. After 5 years, 23 patients were still in group 2, including 5 who had first been in group 1.

Tumor response was seen in 41 patients (76%) in group 2 and 29 (54%) in group 1. Five-year progression-free survival (PFS, time from treatment until death from any cause) was 13% for group 2. In patients who showed a complete response to treatment (no sign of active disease), 5-year PFS was 40%.

Average 5-year overall survival (time from treatment until death from any cause) was 28%. Five-year OS was longer in patients with normal lactate dehydrogenase levels (45%, an indicator in the blood of body tissue damage) at the start of treatment. OS was also improved for patients with normal lactate dehydrogenase and less than three sites of cancer spread (51%).

Fever was the most common negative side effect reported in 69% of the patients from group 2. 

This study suggests that dabrafenib plus trametinib improves the outcomes of metastatic BRAF-mutated melanoma with manageable side effects.