In a nutshell
This review examined the effectiveness of dabrafenib (Tafinlar) and trametinib (Mekinist) for BRAF mutated melanoma with brain metastasis. Researchers concluded that this combined treatment is an important therapy option for patients with advanced melanoma.
Some melanoma patients have a mutation (permanant change) in the BRAF gene. BRAF inhibitors (such as dabrafenib) are used to treat these tumors. Over time, patients can become resistant to this treatment. This resistance happens due to the reactivation of MAPK, a specific protein that allows tumor growth. Therefore, the addition of trametinib (MAKP inhibitor) could help to overcome BRAF resistance. Prior studies showed that this combined therapy improves the treatment of BRAF melanomas without brain metastasis. However, this combined treatment has never been studied in patients with active brain metastasis.
Methods & findings
This review analyzed the effectiveness and toxicity of dabrafenib combined with trametinib in patients with BRAF-mutated melanoma brain metastasis.
125 patients with BRAF-mutated melanoma and brain metastasis were assigned to four different groups. 76 patients in group A had not had previous brain therapy. 16 patients in group B had undergone prior brain therapy. 16 patients in group C were not experiencing symptoms associated with their melanoma. The 17 patients in group D were experiencing some symptoms.
Patients received oral dabrafenib and trametinib until disease progression, death or serious side effects. The average follow up time was 8.5 months.
58% of patients in group A had a response to treatment (such as brain tumor shrinkage). 56% of the patients in group B, 44% in group C and 59% in group D showed a response to treatment.
The most common non-severe side effects were fever (6%) and decreased ejection fraction (heart condition; 4%). The severe effects were fever (3%) and headache (2%).
The bottom line
This study suggested that dabrafenib plus trametinib was active against melanoma brain metastasis with manageable side effects.
The fine print
Groups B, C and D had a limited number of patients.
Published By :
The Lancet. Oncology
Jun 01, 2017