Acneiform eruptions: a common cutaneous toxicity of the MEK inhibitor trametinib

Australas J Dermatol. 2014 Nov;55(4):250-4. doi: 10.1111/ajd.12124. Epub 2013 Dec 9.

Abstract

Background: The MEK inhibitor trametinib is currently undergoing clinical trials as the treatment of metastatic melanoma both alone and in combination with the BRAF inhibitor dabrafenib. One of the most frequent side-effects associated with its use as a single agent is the development of acneiform eruptions. These eruptions seem to be reduced when dosed in combination with dabrafenib.

Objectives: To investigate the prevalence of acneiform eruptions in patients taking the MEK inhibitor trametinib, both alone and in combination with dabrafenib.

Methods: All patients enrolled in the trametinib alone (n = 13) or trametinib and dabrafenib combination (n = 30) clinical trials at a single site underwent a retrospective file review. The development and management of acne or acneiform eruptions was noted.

Results: In total, 77% of the trametinib group developed an acneiform eruption on the trial, while only 10% developed acneiform lesions in the combination trial. The patients were treated with oral doxycycline, topical antibiotics or topical antiseptic washes, with a good response. However the condition recurred if these treatments were ceased and the patient was still on trametinib therapy.

Conclusions: The MEK inhibitor trametinib is associated with the development of acneiform eruptions. When combined with dabrafenib the frequency of this side-effect is reduced.

Keywords: BRAF inhibitor; MEK inhibitor; acneiform eruption; dabrafenib; melanoma; trametinib.

MeSH terms

  • Acneiform Eruptions / chemically induced*
  • Acneiform Eruptions / drug therapy
  • Administration, Cutaneous
  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents, Local / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Clindamycin / administration & dosage
  • Clinical Trials as Topic
  • Doxycycline / therapeutic use
  • Drug Eruptions / drug therapy
  • Drug Eruptions / etiology*
  • Female
  • Humans
  • Imidazoles / administration & dosage
  • Male
  • Melanoma / drug therapy
  • Melanoma / secondary
  • Middle Aged
  • Oximes / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Pyridones / administration & dosage
  • Pyridones / adverse effects*
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / adverse effects*
  • Retrospective Studies
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / pathology
  • Triclosan / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents, Local
  • Imidazoles
  • Oximes
  • Protein Kinase Inhibitors
  • Pyridones
  • Pyrimidinones
  • trametinib
  • Clindamycin
  • Triclosan
  • Doxycycline
  • dabrafenib