Small cell transformation in a patient with BRAF V600E-mutated advanced non-small cell lung cancer

Non-small cell lung cancer (NSCLC) with a BRAF V600E mutation is rare and associated with a worse prognosis compared with wild-type BRAF. The first-line treatment options include a combination of a BRAF inhibitor and a MEK inhibitor or immunotherapy with or without chemotherapy. Unlike advanced NSCLC with common EGFR mutations or ALK rearrangements, the mechanisms of resistance are poorly understood. We report a case of small cell transformation after treatment with a BRAF inhibitor and a MEK inhibitor, which illustrates one potential resistance mechanism. We extrapolated therapeutic data from de novo small cell lung cancer to this case. However, the outcome was unsatisfactory.