Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma

• Published in: Journal of the American Academy of Dermatology Vol. 71; no. 6; pp. 1102 - 1109.e1
• Main Authors: Sanlorenzo, Martina, MD, Choudhry, Aditi, MD, Vujic, Igor, MD, Posch, Christian, MD, Chong, Kim, MD, Johnston, Katia, BSc, Meier, Melissa, MD, Osella-Abate, Simona, MSc, Quaglino, Pietro, MD, Daud, Adil, MD, Algazi, Alain, MD, Rappersberger, Klemens, MD, Ortiz-Urda, Susana, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2014
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Azetidines - administration & dosage; Azetidines - adverse effects; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - mortality; cutaneous adverse event; Dermatology; Female; Follow-Up Studies; histology; Humans; Imidazoles - administration & dosage; Imidazoles - adverse effects; Indoles - administration & dosage; Indoles - adverse effects; inflammation; Kaplan-Meier Estimate; Male; Melanoma - drug therapy; Melanoma - mortality; Middle Aged; Oximes - administration & dosage; Oximes - adverse effects; Piperidines - administration & dosage; Piperidines - adverse effects; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Proto-Oncogene Proteins B-raf - antagonists & inhibitors; Pyridones - administration & dosage; Pyridones - adverse effects; Pyrimidinones - administration & dosage; Pyrimidinones - adverse effects; rash; Retrospective Studies; Skin Neoplasms - drug therapy; Skin Neoplasms - mortality; squamous cell carcinoma; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; therapy; Young Adult; FDA; keratoacanthoma; twice a day; therapy; CI; BRAF inhibitor; AK; MEK inhibitor; MAPK; actinic keratosis; cutaneous adverse event; mitogen-activated protein kinase; rash; MEKi; SCC; histology; inflammation; KA; confidence interval; bid; BRAFi; Food and Drug Administration; squamous cell carcinoma
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2014.09.002

Background BRAF inhibitor (BRAFi) and MEK inhibitor (MEKi) frequently cause cutaneous adverse events. Objective We sought to investigate the cutaneous safety profile of BRAFi versus BRAFi and MEKi combination regimens. Methods We performed a retrospective cohort study, collecting data from 44 patients with melanoma treated either with BRAFi (vemurafenib or dabrafenib) or BRAFi and MEKi combination regimens (vemurafenib + cobimetinib or dabrafenib + trametinib). Patient characteristics, and the occurrence and severity of cutaneous adverse events, are described. Results The development of cutaneous adverse events was significantly less frequent ( P  = .012) and occurred after longer treatment time ( P  = .025) in patients treated with BRAFi and MEKi combination regimen compared with patients treated with BRAFi monotherapy. Among patients who received both BRAFi and the combination of BRAFi and MEKi at different time points during their treatment course, the development of squamous cell carcinoma or keratoacanthoma was significantly less frequent when they received the combination regimen ( P  = .008). Patients receiving vemurafenib developed more cutaneous adverse events ( P  = .001) and in particular more photosensitivity ( P  = .010) than patients who did not. Limitations There were a limited number of patients. Conclusion Combination regimen with BRAFi and MEKi shows fewer cutaneous adverse events and longer cutaneous adverse event-free interval compared with BRAFi monotherapy.