Cutaneous effects of BRAF inhibitor therapy: a case series

Ann Oncol. 2013 Feb;24(2):530-537. doi: 10.1093/annonc/mds292. Epub 2012 Oct 3.

Abstract

Background: The cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors are not well understood. Squamous cell carcinoma (SCC), keratoacanthoma, and photosensitivity have been described in patients taking BRAF inhibitors.

Patients and methods: To characterize the timing and frequency of skin lesions in patients receiving BRAF inhibitor therapy, we utilized a retrospective case review of 53 patients undergoing treatment with BRAF inhibitors for 4-92 weeks of therapy. Patients were evaluated at baseline, and then followed at 4- to 12-week intervals. Charts were retrospectively reviewed, and the morphology and timing of cutaneous events were recorded.

Results: Thirty-three of the 53 charts met exclusion/inclusion criteria, 15 were treated with vemurafenib, and 18 were treated with GSK 2118436/GSK 1120212. Of 33 patients treated with BRAF inhibitor, 13 developed photosensitivity (39.4%), 10 developed actinic keratoses (30.3%), 10 developed warts (30.3%), and 6 developed SCC (18.2%).

Conclusions: Multiple cutaneous findings were observed in the 33 patients taking BRAF inhibitors. The previously described association with SCC and photosensitivity was observed in these patients as well. Over half of the observed SCCs were invasive in nature. Photosensitivity continues to be frequent with BRAF inhibitors. Patients taking BRAF inhibitors should have regular full body skin exams. Further studies are necessary to better elucidate the rates of these adverse cutaneous effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Squamous Cell / chemically induced
  • Female
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use
  • Indoles / adverse effects
  • Indoles / therapeutic use
  • Keratoacanthoma / chemically induced
  • Keratosis, Actinic / chemically induced
  • Male
  • Melanoma / drug therapy
  • Middle Aged
  • Neoplasms / drug therapy*
  • Oximes / adverse effects
  • Oximes / therapeutic use
  • Photosensitivity Disorders / chemically induced
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Pyridones / adverse effects
  • Pyridones / therapeutic use
  • Pyrimidinones / adverse effects
  • Pyrimidinones / therapeutic use
  • Retrospective Studies
  • Skin Diseases / chemically induced*
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use
  • Vemurafenib
  • Warts / chemically induced

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Indoles
  • Oximes
  • Pyridones
  • Pyrimidinones
  • Sulfonamides
  • Vemurafenib
  • trametinib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • dabrafenib