Cutaneous adverse events in patients treated with BRAF inhibitor-based therapies for metastatic melanoma for longer than 52 weeks

Br J Dermatol. 2015 Jan;172(1):239-43. doi: 10.1111/bjd.13200. Epub 2014 Nov 21.

Abstract

Background: BRAF inhibitor-based therapies have been shown to induce cutaneous toxicities, with onset generally in the first 8-26 weeks of therapy.

Objectives: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Drug Eruptions / etiology*
  • Female
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects*
  • Indoles / administration & dosage
  • Indoles / adverse effects*
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • Male
  • Melanoma / drug therapy*
  • Middle Aged
  • Neoplasm Metastasis
  • Oximes / administration & dosage
  • Oximes / adverse effects*
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Pyridones / administration & dosage
  • Pyridones / adverse effects
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / adverse effects
  • Skin Neoplasms / drug therapy*
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects*
  • Vemurafenib

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Indoles
  • Oximes
  • Protein Kinase Inhibitors
  • Pyridones
  • Pyrimidinones
  • Sulfonamides
  • Vemurafenib
  • trametinib
  • MAP Kinase Kinase Kinases
  • dabrafenib