title: Response of BRAF inhibitor-associated squamous cell lung carcinoma to drug withdrawal.
abstract: Vemurafenib and dabrafenib, two Food and Drug Administration-approved selective BRAF kinase inhibitors (BRAFi), have revolutionized the targeted therapy of cutaneous melanoma. Off-target effects of these drugs paradoxically activate the MAP kinase pathway in BRAF wild-type cells, leading to secondary malignancies. Although cutaneous squamous cell carcinomas are by far the most frequent, emergence of potentially life-threatening secondary tumors from other sites following prolonged therapy is a growing concern. Herein, we provide the first case report of squamous cell lung carcinoma apparently secondary to BRAFi developing in a metastatic melanoma patient on vemurafenib for 23 months. Subsequent BRAFi with dabrafenib for 5 months was accompanied by rapid lung cancer progression with 86% increase in diameter. Withdrawal of BRAFi as the only change in therapy resulted in partial response maintained for more than 8 months. Clinicians should be atuned to the risk of noncutaneous second malignancies induced by BRAFi, particularly in the setting of progression of an isolated lesion after prolonged therapy.
authors.affiliation: aCovenant College, Lookout Mountain, Georgia bComprehensive Cancer Center cDivision of Hematology Oncology, University of Alabama dDepartment of Radiology, General Radiology and Cardiopulmonary Section, UAB Medicine, Birmingham, Alabama, USA.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Blackmon
authors.forename: Ratika
authors.initials: R
authors.lastname: Dhawan
authors.forename: Nina L
authors.initials: NL
authors.lastname: Terry
authors.forename: Robert M
authors.initials: RM
authors.lastname: Conry
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D000074324:Ipilimumab / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy* / Q000601:surgery; D010091:Oximes / Q000008:administration & dosage; D000072078:Positron Emission Tomography Computed Tomography; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D066066:Response Evaluation Criteria in Solid Tumors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D013449:Sulfonamides / Q000008:administration & dosage; D000077484:Vemurafenib; D028761:Withholding Treatment
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007093:Imidazoles; D007211:Indoles; D000074324:Ipilimumab; D010091:Oximes; D013449:Sulfonamides; D000077484:Vemurafenib; C582435:pembrolizumab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib