title: Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma.
abstract: BACKGROUND
  BRAF inhibitor (BRAFi) and MEK inhibitor (MEKi) frequently cause cutaneous adverse events.
  
  
  OBJECTIVE
  We sought to investigate the cutaneous safety profile of BRAFi versus BRAFi and MEKi combination regimens.
  
  
  METHODS
  We performed a retrospective cohort study, collecting data from 44 patients with melanoma treated either with BRAFi (vemurafenib or dabrafenib) or BRAFi and MEKi combination regimens (vemurafenib + cobimetinib or dabrafenib + trametinib). Patient characteristics, and the occurrence and severity of cutaneous adverse events, are described.
  
  
  RESULTS
  The development of cutaneous adverse events was significantly less frequent (P = .012) and occurred after longer treatment time (P = .025) in patients treated with BRAFi and MEKi combination regimen compared with patients treated with BRAFi monotherapy. Among patients who received both BRAFi and the combination of BRAFi and MEKi at different time points during their treatment course, the development of squamous cell carcinoma or keratoacanthoma was significantly less frequent when they received the combination regimen (P = .008). Patients receiving vemurafenib developed more cutaneous adverse events (P = .001) and in particular more photosensitivity (P = .010) than patients who did not.
  
  
  CONCLUSIONS
  There were a limited number of patients.
  
  
  CONCLUSIONS
  Combination regimen with BRAFi and MEKi shows fewer cutaneous adverse events and longer cutaneous adverse event-free interval compared with BRAFi monotherapy.
authors.affiliation: University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California; Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy. Electronic address: martina.sanlorenzo@hotmail.it.
authors.forename: Martina
authors.initials: M
authors.lastname: Sanlorenzo
authors.affiliation: University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
authors.forename: Aditi
authors.initials: A
authors.lastname: Choudhry
authors.affiliation: University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California; Department of Dermatology, Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
authors.forename: Igor
authors.initials: I
authors.lastname: Vujic
authors.affiliation: University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California; Department of Dermatology, Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Posch
authors.affiliation: University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
authors.forename: Kim
authors.initials: K
authors.lastname: Chong
authors.affiliation: University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
authors.forename: Katia
authors.initials: K
authors.lastname: Johnston
authors.affiliation: University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
authors.forename: Melissa
authors.initials: M
authors.lastname: Meier
authors.affiliation: Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Osella-Abate
authors.affiliation: Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Quaglino
authors.affiliation: University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
authors.forename: Adil
authors.initials: A
authors.lastname: Daud
authors.affiliation: University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
authors.forename: Alain
authors.initials: A
authors.lastname: Algazi
authors.affiliation: Department of Dermatology, Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
authors.forename: Klemens
authors.initials: K
authors.lastname: Rappersberger
authors.affiliation: University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
authors.forename: Susana
authors.initials: S
authors.lastname: Ortiz-Urda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001384:Azetidines / Q000008:administration & dosage / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D010091:Oximes / Q000008:administration & dosage / Q000009:adverse effects*; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D000077484:Vemurafenib; D055815:Young Adult
chemical_list: D001384:Azetidines; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; D013449:Sulfonamides; D000077484:Vemurafenib; C560077:trametinib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C574276:cobimetinib; C561627:dabrafenib
keywords: cutaneous adverse event; histology; inflammation; rash; squamous cell carcinoma; therapy