title: Ocular toxicity in BRAF mutant cutaneous melanoma patients treated with vemurafenib.
abstract: OBJECTIVE
  To determine the frequency of ocular adverse effects associated with vemurafenib (PLX4032) treatment for metastatic cutaneous melanoma.
  
  
  METHODS
  Retrospective review of the clinical study reports from the clinical pharmacology, phase 1, phase 2, and phase 3 trials of vemurafenib.
  
  
  METHODS
  The vemurafenib clinical trials were a multicenter series involving adult patients with histologically confirmed, BRAF(V600) mutation-positive, unresectable, stage IIIC or IV melanoma. A total of 855 patients were enrolled in the trials: 568 patients were treated with vemurafenib and 287 patients were treated with dacarbazine.
  
  
  RESULTS
  Among the 568 patients treated with vemurafenib, ocular adverse effects developed in 22% (95% confidence interval [CI], 18.5-25.6). The most common ocular diagnosis was uveitis (4.0%; 95% CI, 2.6-6.0), followed by conjunctivitis (2.8%; 95% CI, 1.6-4.5) and dry eyes (2.0%; 95% CI, 1.1-3.7). All were successfully managed while vemurafenib therapy was continued.
  
  
  CONCLUSIONS
  Ocular adverse events and symptoms may be seen in more than one-fifth of patients being treated with vemurafenib. However, vemurafenib can be continued while the ocular symptoms are being managed. The pathogenesis of ocular symptoms in this patient population is unclear; additional studies are necessary.
authors.affiliation: Departments of Ophthalmology and the Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Christina H
authors.initials: CH
authors.lastname: Choe
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.affiliation: Genentech, South San Francisco, California.
authors.forename: Ivor
authors.initials: I
authors.lastname: Caro
authors.affiliation: Departments of Ophthalmology and the Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: John H
authors.initials: JH
authors.lastname: Kempen
authors.affiliation: Department of Medicine, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Electronic address: ravi.amaravadi@uphs.upenn.edu.
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Amaravadi
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D003231:Conjunctivitis / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D003606:Dacarbazine / Q000627:therapeutic use; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D005128:Eye Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013449:Sulfonamides / Q000009:adverse effects*; D014605:Uveitis / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D000077484:Vemurafenib; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D003606:Dacarbazine; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf