Dramatic Response to Sequential BRAF Inhibition in BRAF V600E–Mutant Metastatic Lung Adenocarcinoma

Lung[AQ1][AQ2] cancer is the leading cause of cancerrelated death.1 Targeted therapy directed toward molecular pathways that drive non–small-cell lung cancer (NSCLC) has dramatically improved treatment options. Some of the oncogenic drivers identified in lung adenocarcinoma involve the RAS-RAF-mitogen-activated protein kinase (MAPK) kinase (MEK)-extracellular regulated kinase (ERK) pathway (MAPK-ERK pathway).2 BRAF is a key protein in MAPK-ERK signaling. Mutations in BRAF[AQ3] are present in 1% to 3% of NSCLC and lead to constitutive activation of the MAPK-ERK pathway, promoting cancer cell proliferation and survival. Substitution of valine with glutamatic acid at codon 600 of exon 15 (V600E) is the most common BRAF mutation (approximately 50%) in NSCLC. Several other mutations of BRAF have been identified and are grouped as non-V600E mutations.3 Patients with NSCLC harboring BRAF V600E mutations are sensitive to BRAF inhibitors (BRAFis) alone or in combination with MEK inhibitors (MEKis).4-6 After initial response, patients typically experience relapse as a result of various resistance mechanisms. Treatment after progression is not well defined. In this report, we present a case of a patient who achieved a significant response with dabrafenib and trametinib after initial progression on vemurafenib.