Efficacy of pembrolizumab in lung adenocarcinoma harboring non-V600E BRAF mutation: a case report

Small percentage of non-small cell lung cancer (NSCLC) patients, ranging 2–4% present BRAF mutations whom classification is easily accounted as V600E/non-V600E variant. There is a growing interest linked to different functional classes of BRAF mutations, which include class I (V600E mutations), class II mutations (kinase-activating non-V600E mutations), and class III mutations (kinase-impaired non-V600E mutations that increase ERK signaling or RAS activity), with a more aggressive behavior in non-V600E mutant NSCLC. V600E positive mutation patients are susceptible to target therapies, as the combination dabrafenib and trametinib in first- and second-line setting; meanwhile the others have an unknown clinical significance and there is no standard of therapy. Higher levels of programmed death-ligand 1 (PD-L1) expression are associated with presence of BRAF mutation. Furthermore, there is little evidence on the efficacy of immune checkpoint inhibitors (ICIs): in contrast to EGFR mutated or ALK rearranged tumors, ICIs have favorable activity both in V600E than non-V600E mutated BRAF variant. We identified a biological rationale for the use of immunotherapy in patients harboring uncommon BRAF mutations. We report a case of a G466E BRAF-mutated lung adenocarcinoma successfully treated with pembrolizumab. Besides, our case adds to the limited literature on NSCLC harboring BRAF mutations, showing the importance of analyze the biological significance of specific BRAF mutation before starting a treatment.