Long-Term Outcomes With BRAF and MEK Inhibition in BRAF V600–Mutant Metastatic Melanoma


Key Points

  • In patients receiving dabrafenib and trametinib for BRAF V600–mutant metastatic melanoma, overall survival was 30% at 4 years and 28% at 5 years.
  • Survival was higher among patients with a normal baseline LDH level.

As reported by Long et al in the Journal of Clinical Oncology, a 5-year landmark analysis of patients receiving dabrafenib (Tafinlar) and trametinib (Mekinist) for BRAF V600–mutant metastatic melanoma shows persistent overall and progression-free survival benefits.

Study Details

The analysis included 54 patients who received dabrafenib at 150 mg twice daily plus trametinib at 2 mg once daily in a phase II trial (BRF113220) and 45 patients who crossed over to this regimen after disease progression on dabrafenib monotherapy.

Long-Term Outcomes

At the time of analysis (October 2016), 18 patients receiving the combination remained in the study, including 13 of 54 patients (24%) initially enrolled at this dose and 5 of 45 patients (11%) who crossed over to the combination treatment. Among all patients receiving the regimen, overall survival was 30% at 4 years and 28% at 5 years, and progression-free survival was 13% at both 4 and 5 years. Overall survival at 5 years was 45% in patients with a normal lactate dehydrogenase (LDH) level at baseline and 51% in those with a normal LDH and up to three organ sites with metastasis. Over extended follow-up, one patient improved from a partial to a complete response.

The investigators concluded: “This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600-mutant [metastatic melanoma]. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term [overall survival] and progression-free survival that last ≥ 5 years in some patients with [metastatic melanoma].

The study was supported by GlaxoSmithKline. Dabrafenib and trametinib are assets of Novartis as of March 2015.

Georgina V. Long, MBBS, PhD, of Melanoma Institute Australia, University of Sydney, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.