title: Acneiform eruption in a patient with metastatic melanoma after ceasing combination dabrafenib/trametinib therapy.
abstract: BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) increase survival in BRAF mutant metastatic melanoma patients; however, they induce a well-known spectrum of cutaneous side effects during treatment. Whereas the BRAFi dabrafenib induces cutaneous squamous cell carcinomas and verrucal keratosis, the MEKi trametinib frequently induces acneiform eruptions that are reversible after drug discontinuation. Furthermore, when dabrafenib and trametinib are used in combination, there are fewer cutaneous toxicities. We report a patient with BRAF mutant metastatic melanoma treated with the BRAFi/MEKi combination therapy who developed an acneiform eruption after treatment discontinuation rather than during active therapy. Moreover, the eruption resolved when the combination treatment was reintroduced and recurred after increasing the dose of trametinib. The eruption may be explained by the longer half-life of trametinib (4.5 days) compared with dabrafenib (5.2 h). This is the first case reported with this particular side effect induced after stopping the treatment and could become more frequent as the BRAFi/MEKi combination of drugs is more frequently prescribed.
authors.affiliation: Departments of aDermatology bMedical Oncology, Westmead Hospital cSydney Medical School, The University of Sydney dMelanoma Institute Australia, Sydney, New South Wales, Australia eDepartment of Dermatology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Uribe
authors.forename: Rachael M
authors.initials: RM
authors.lastname: Anforth
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.forename: Pablo
authors.initials: P
authors.lastname: Fernandez-Peñas
mesh_terms: D017486:Acneiform Eruptions / Q000139:chemically induced / Q000150:complications*; D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D017809:Fatal Outcome; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008545:Melanoma / Q000150:complications* / Q000188:drug therapy; D009154:Mutation; D009362:Neoplasm Metastasis; D010091:Oximes / Q000008:administration & dosage*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D011728:Pyridones / Q000008:administration & dosage*; D011744:Pyrimidinones / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000150:complications* / Q000188:drug therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007093:Imidazoles; D010091:Oximes; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib