Adding to the targeted therapy toolbox: BRAF and MEK inhibition in the treatment of BRAF V600E metastatic non-small cell lung cancer

Mutations in the BRAF oncogene are found in approximately 2–4% of non-small cell lung cancer (NSCLC). The most common mutation is associated with substitution of glutamic acid for valine at position 600 (V600E) within the BRAF kinase. Targeted therapy against the BRAF V600E mutant kinase has shown efficacy in other solid tumors including melanoma. In this setting, dual inhibition of both BRAF and the downstream mitogen-activated protein kinase kinase (MEK) improves survival compared to BRAF inhibition alone. Planchard et al. published two recent phase 2 trials evaluating the clinical activity and safety profile of second-line BRAF monotherapy (dabrafenib) and BRAF-MEK combination therapy (dabrafenib plus trametinib), respectively, in patients with stage IV BRAF V600E mutant NSCLC. Here, we review the pertinent findings from each of these studies, discuss their significance in context of the current literature, and consider their potential impact on the management of patients with NSCLC in the clinical setting.