title: Vemurafenib beyond progression in a patient with metastatic melanoma: a case report.
abstract: The prognosis of metastatic melanoma has changed markedly in recent years because of the advent of newer targeted therapies such as BRAF inhibitors. However, the response to BRAF inhibitor therapy is frequently nondurable in patients with advanced melanoma. Novel approaches are thus needed to overcome resistance to these agents and to improve the management of advanced melanoma patients after disease progression. Here, we present the case of a 44-year-old man diagnosed with advanced melanoma in July 2010, harboring a BRAF mutation. Melanoma progressed during first-line chemotherapy with dacarbazine, but showed significant benefit after the initiation of vemurafenib on August 2011. Six months later, the patient experienced disease progression in left-obturator lymphadenopathy; still, anti-BRAF treatment was continued together with stereotactic radiotherapy, and was interrupted only shortly for intestinal occlusion secondary to melanoma metastasis of the bowel. When his conditions were stable, after 1 month of vemurafenib treatment discontinuation, anti-BRAF therapy was reinitiated, with a positive outcome. Vemurafenib treatment was definitively discontinued for disease progression in the brain, peritoneum, lymph node, intestine, and skin in March 2013, after about 20 months from initiation, and the patient died a few weeks later. The clinical case presented here shows that treatment beyond progression with vemurafenib can yield a survival benefit in melanoma patients whose disease progresses in a few sites, which can be treated with locoregional therapies. This clinical strategy needs further validation in prospective clinical trials.
authors.affiliation: aDivision of Melanoma, Cancer Immunotherapy and Innovative Therapies bDivision of Melanoma and Skin Cancer cDepartment of Diagnostic Imaging, Radiant and Metabolic Therapy, Division of Radiology dDivision of Radiotherapy, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Grimaldi
authors.forename: Ester
authors.initials: E
authors.lastname: Simeone
authors.forename: Marco
authors.initials: M
authors.lastname: Palla
authors.forename: Lucia
authors.initials: L
authors.lastname: Festino
authors.forename: Corrado
authors.initials: C
authors.lastname: Caracò
authors.forename: Nicola
authors.initials: N
authors.lastname: Mozzillo
authors.forename: Antonella
authors.initials: A
authors.lastname: Petrillo
authors.forename: Paolo
authors.initials: P
authors.lastname: Muto
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017809:Fatal Outcome; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use*; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf