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Ref Type Journal Article
PMID (35135105)
Authors Chae YK, Tamragouri KB, Chung J, Lin X, Miller V, Ali SM, Giles FJ
Title Large-Cell Neuroendocrine Carcinoma of the Lung: A Focused Analysis of BRAF Alterations and Case Report of a BRAF Non-V600-Mutated Tumor Responding to Targeted Therapy.
Journal Vol Issue Date Pages Journal Short Title
JCO precision oncology 2 2018 Nov 1-12 JCO Precis Oncol
URL
Abstract Text In advanced stages, large-cell neuroendocrine carcinoma of the lung (L-LCNEC) mimics small-cell lung cancer despite its traditional classification as a non-small-cell lung cancer. Here we present a focused analysis of BRAF mutations in this population.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.In 13 patients, 14 unique BRAF alterations (amplifications, mutations) were identified. The importance of biomarker-driven therapy is subsequently highlighted with our case of a 69-year-old man diagnosed with metastatic L-LCNEC who did not respond to cisplatin plus etoposide. A significant durable response was then demonstrated with therapy targeted toward a BRAF non-V600E activating mutation (G469R) associated with biomarker response identified through circulating cell-free tumor DNA analysis. A change in clonal allele frequency from nearly 40% to nondetectable was observed.Although uncommon, L-LCNEC does seem to contain activating and therefore actionable alterations. We thus highlight the value of pursuing next-generation sequencing for patients with this disease.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF G469R large cell neuroendocrine carcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a durable response in a patient with large cell neuroendocrine carcinoma of the lung harboring BRAF G469R, along with ERBB4 (HER4) A118S, STK11 L282fs, TP53 R248L and MYC amplification and led to a decrease in BRAF G469R in cell-free DNA (PMID: 35135105). 35135105