title: BRAFV600 mutant non-small-cell lung cancer resistant to Vemurafenib.
abstract: Vemurafenib has shown significant activity in V600 mutant melanoma; however the role of this agent in Lung adenocarcinoma with an activating BRAF mutation is still evolving. One of our patients had a rare activating BRAF mutation detected through tumor exome sequencing, which led to a switch from her successful therapy to Vemurafenib and ultimately tumor progression. The lack of adequate response was disappointing both in terms of lost disease free survival and heavy financial burden to the patient who had to cover the charges of her unsuccessful off-label therapy. This experience, despite its highlight of treatment failure, puts into question the use of next generation sequencing and the trend for using off-label agents in pursuit of an optimal response without the support of strong clinical evidence.
authors.affiliation: Department of Hematology Oncology, Faculty of Medicine, Saint Joseph University Beirut, Lebanon.
authors.forename: Fadi
authors.initials: F
authors.lastname: El Karak
authors.affiliation: Department of Hematology Oncology, Faculty of Medicine, Saint Joseph University Beirut, Lebanon.
authors.forename: Tarek
authors.initials: T
authors.lastname: Assi
authors.affiliation: Department of Hematology Oncology, Faculty of Medicine, Saint Joseph University Beirut, Lebanon.
authors.forename: Hampig Raphael
authors.initials: HR
authors.lastname: Kourie
authors.affiliation: Department of Hematology Oncology, Faculty of Medicine, Saint Joseph University Beirut, Lebanon.
authors.forename: Elie
authors.initials: E
authors.lastname: El Rassy
authors.affiliation: Department of Hematology Oncology, Faculty of Medicine, Saint Joseph University Beirut, Lebanon.
authors.forename: Ralph
authors.initials: R
authors.lastname: Chebib
authors.affiliation: Department of Hematology Oncology, Faculty of Medicine, Saint Joseph University Beirut, Lebanon.
authors.forename: Maya
authors.initials: M
authors.lastname: Ghor
authors.affiliation: Department of Hematology Oncology, Faculty of Medicine, Saint Joseph University Beirut, Lebanon.
authors.forename: Samer
authors.initials: S
authors.lastname: Tabchi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D004252:DNA Mutational Analysis; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D057915:Drug Substitution; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D064847:Multimodal Imaging / Q000379:methods; D009154:Mutation; D056687:Off-Label Use; D010641:Phenotype; D049268:Positron-Emission Tomography; D057285:Precision Medicine; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013449:Sulfonamides / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF mutation; Lung Adenocarcinoma; Vemurafenib; next generation sequencing