Combined BRAF and MEK inhibition in BRAF -mutant NSCLC

The trial included only patients with the BRAFV600E mutation (a glutamate for valine substitution at codon 600), which is present in 70-90% of BRAF-mutated melanomas but in only 50-60% of BRAF-mutated NSCLC.2,3 The rationale for combining BRAF and MEK inhibition is to reduce the paradoxical upregulation in MAPK signalling recorded with single-drug BRAF inhibitor, and has been shown, in phase 3 melanoma trials,4 to deliver improved responses, a reduction in adverse effects related to increased MAPK signalling (eg, cutaneous squamous cell carcinoma and keratoacanthoma), and delayed development of resistance to treatment.