Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib.
BACKGROUND
Dabrafenib, a novel selective small-molecule inhibitor of BRAF, has been shown to increase overall survival in patients with unresectable metastatic melanoma harboring the BRAF V600E mutation. The development of resistance has led to combination therapy with selective MEK inhibitor trametinib. Compared with vemurafenib, dabrafenib is a more recent BRAF inhibitor approved by the Food and Drug Administration in May 2013 for metastatic melanoma; fewer data are available in the current literature regarding cutaneous toxicity.


OBJECTIVE
We sought to present additional cutaneous side effects of dabrafenib and trametinib and follow their evolution and management.


METHODS
We carried out a prospective study of 14 patients treated with dabrafenib alone or with trametinib. Patients were followed every 4 weeks, and we collected detailed cutaneous symptoms, photos, and biopsy specimens.


RESULTS
All patients presented with at least 1 adverse skin reaction. The mean duration of treatment was 24 weeks. The most common adverse effect was papillomas (7/14), followed by palmoplantar hyperkeratosis (5/14), alopecia (5/14), and seborrheic dermatitis-like eruption (2/14). Three patients who received trametinib developed an acneiform eruption (3/5). One patient developed a keratoacanthoma-like squamous cell carcinoma. Side effects presented as early as 2 weeks after starting therapy, with a mean time of onset of 9 weeks.


CONCLUSIONS
Selective BRAF inhibitor dabrafenib and MEK inhibitor trametinib are associated with multiple skin adverse effects. Given their recent approval and the potential for malignant lesions to develop on treatment, awareness of potential adverse effects and their management is necessary.
1 McGill University, Division Dermatology, Montréal, QC, Canada.
Jean-Philip
JP
Lacroix
1 McGill University, Division Dermatology, Montréal, QC, Canada.
Beatrice
B
Wang
D017486:Acneiform Eruptions / Q000139:chemically induced; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D012628:Dermatitis, Seborrheic / Q000139:chemically induced; D003875:Drug Eruptions / Q000209:etiology*; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007645:Keratoderma, Palmoplantar / Q000139:chemically induced; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary; D008875:Middle Aged; D010091:Oximes / Q000008:administration & dosage / Q000009:adverse effects*; D010212:Papilloma / Q000139:chemically induced*; D011446:Prospective Studies; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology
D007093:Imidazoles; D010091:Oximes; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; C561627:dabrafenib
cancer; drug reaction; melanoma; pathology