Reply to M. Perier-Muzet et al
Authors: Lisa Zimmer, Lauren E. Haydu, Alexander M. Menzies, Richard A. Scolyer, Richard F. Kefford, John F. Thompson, Dirk Schadendorf, Georgina V. Long
Journal: Journal of Clinical Oncology (2014)

We thank Perier-Muzet et al 1 for their comments regarding the importance of adequate dermatologic surveillance in patients with melanoma treated with a BRAF inhibitor in the adjuvant setting.We agree that the use of conventional dermoscopy (not digital dermoscopy) should be the standard of dermatologic assessment for examining pigmented skin lesions.Recently, Perier-Muzet et al 2 reported a high rate of dermoscopic changes occurring on melanocytic lesions of patients receiving the BRAF inhibitor vemurafenib.They pointed out that almost all of the changes were observed by digital dermoscopy and were not visible by naked-eye examination.However, conventional, analog dermoscopy, which is used more commonly than digital dermoscopy in daily routine practice, was not used as a control.It remains unclear whether digital dermoscopy is superior to analog dermoscopy in identifying new primary melanomas (NPMs) in patients treated with vemurafenib.Perier-Muzet et al 1 argued that the true effect of BRAF inhibitors on the incidence of NPMs will not be assessed in the randomized placebo-controlled adjuvant clinical trial of vemurafenib (A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Vemurafenib [RO5185426] Adjuvant Therapy in Patients With Surgically Resected, Cutaneous BRAF Mutant Melanoma at High Risk for Recurrence [BRIM8]; NCT01667419) because of the lack of protocol-driven dermoscopic surveillance.The BRIM8 protocol requires dermatologic assessment by a designateddermatologistwhoisexperiencedinthediagnosisandmanagement ofcutaneousneoplasms.Severalsurveysevaluatedtheuseofconventional dermoscopy by dermatologists in the United States, 3,4 Australia, 5,6 and Europe. 7Surveys published in 2007 5 and 2011 6 of Australian dermatologists found a high prevalence of dermoscopy use, 95% and 98%, respectively.In a US survey, 94% of dermatology chief residents used dermoscopy. 4In a nationwide survey conducted in academic and nonacademic hospital centers in France, 98% reported using dermoscopy. 7aken together, these data suggest that most dermatologists use conventional dermoscopy for examining pigmented lesions.Given that protocol-driven dermatologic surveillance by a dermatologist is required and conventional, and analog dermoscopy is widely used by dermatologists, we adhere to our conclusion that the true effect of BRAF inhibitors on the incidence of NPMs will be assessed in the BRIM8 study.Moreover, regardless of the use of dermoscopy, because the BRIM8 study is a randomized, double-blind, placebo-controlled trial, any important difference in NPM risk should be revealed via any method of dermatologic assessment, as long as the method is consistent between both arms and for a given patient.Furthermore, use of single-agent BRAF inhibition in melanoma may decrease moving forward.The combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib is currently approved for use in V600 BRAF mutant metastatic melanoma in the United States and Australia because of its superior efficacy and fewer onco-genic toxicities compared with dabrafenib, 8 and is under investigation in the adjuvant setting (NCT01682083).