The increased use of next generation sequencing has allowed for a detailed interrogation of the molecular landscape of non-small cell lung cancer (NSCLC), identifying different patient subgroups with therapeutically targetable genetic alterations. In this respect, BRAF-mutant NSCLC represent a small, but non-negligible subgroup of NSCLC patients. Data from a pivotal phase II trial have demonstrated that dual BRAF (dabrafenib) and MEK (trametinib) inhibition has durable antitumor activity in patients with a BRAFV600E mutation, making screening for this specific BRAF alteration a mandatory requirement in the diagnostic work-up of metastatic NSCLC. Unfortunately, however, V600E mutations make up only half of all BRAF mutations in NSCLC and the non-V600 patients currently remain orphan of targeted approaches. This article will provide an overview of the clinical trial data obtained with BRAF inhibitors in BRAF-mutant NSCLC after which some of the remaining clinical challenges will be addressed.
