Molecular landscape of BRAF mutations in large cell neuroendocrine carcinoma of lung: An analysis of BRAF mutations and a case report of a BRAF non-V600E mutated tumor responding to targeted therapy.

11621Background: In advanced stages, large cell neuroendocrine carcinoma of the lung (L-LCNEC) mimics small cell lung cancer (SCLC) despite its traditional classification as a non-small cell lung cancer (NSCLC). Here we present a focused analysis of BRAF mutations in this population. Methods: Comprehensive genomic profiling of tumor tissues was performed from a cohort of 300 patients with biopsy proven L-LCNEC. Specimens were either from a primary lung lesion or metastatic site. Results: 14 unique BRAF alterations (amplifications, mutations) were identified in 13 patients. The importance of biomarker driven therapy is subsequently highlighted with our case of a 69 year-old male diagnosed with metastatic L-LCNEC that did not respond to cisplatin/etoposide. He then demonstrated a significant durable response with therapy targeted toward a BRAF non-V600E mutation (G469R) associated with biomarker response identified through circulating cell free tumor DNA analysis. A change in clonal allele frequency from ne...