title: Cutaneous adverse events in patients treated with BRAF inhibitor-based therapies for metastatic melanoma for longer than 52 weeks.
abstract: BACKGROUND
  BRAF inhibitor-based therapies have been shown to induce cutaneous toxicities, with onset generally in the first 8-26 weeks of therapy.
  
  
  OBJECTIVE
  To determine whether cutaneous toxicities persist in patients who have remained on BRAF inhibitor-based therapies for longer than 52 weeks, and therefore whether ongoing dermatology assessment is required.
  
  
  METHODS
  All patients treated with the BRAF inhibitors vemurafenib or dabrafenib or combination BRAF inhibitor and mitogen-activated protein kinase kinase (MEK) inhibitor therapy at Westmead Hospital, Sydney, Australia underwent regular dermatological assessments for the duration of therapy. All patients enrolled in a clinical trial, and 18% of patients in the compassionate access scheme underwent a baseline assessment prior to commencement of therapy and every 4-8 weeks thereafter. Patients' adverse events were recorded in a specific database.
  
  
  RESULTS
  Patients continued to develop cutaneous adverse events after 52 weeks of continuous therapy. Patients on single-agent BRAF inhibitor therapy suffered from Grover disease (45%), plantar hyperkeratosis (45%), verrucal keratosis (18%) and even cutaneous squamous cell carcinoma (16%). The most frequent adverse event seen in patients in the combination BRAF and MEK inhibitor group was an acneiform eruption (40%).
  
  
  CONCLUSIONS
  Patients on BRAF inhibitor-based therapies need to continue to have regular dermatological follow-up independent of the duration of their therapy.
authors.affiliation: Department of Dermatology, Westmead Hospital, Darcy Rd, Westmead, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Anforth
authors.forename: G
authors.initials: G
authors.lastname: Carlos
authors.forename: A
authors.initials: A
authors.lastname: Clements
authors.forename: R
authors.initials: R
authors.lastname: Kefford
authors.forename: P
authors.initials: P
authors.lastname: Fernandez-Peñas
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D003875:Drug Eruptions / Q000209:etiology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010091:Oximes / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects; D012878:Skin Neoplasms / Q000188:drug therapy*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; D013449:Sulfonamides; D000077484:Vemurafenib; C560077:trametinib; D020930:MAP Kinase Kinase Kinases; C561627:dabrafenib