Eruptive naevi in a patient treated with LGX818 for BRAF mutant metastatic melanoma

Abstract

LGX818 is a new-generation BRAF inhibitor (BRAFi) that is currently undergoing phase 3 trials for the treatment of BRAF mutant metastatic melanoma patients (NCT01909453). Cutaneous toxicities associated with the administration of BRAF inhibitors are considered to be induced by the paradoxical activation of the mitogen-activated protein kinase pathway in wild-type BRAF cells. Changes in naevi, including new naevi, hyperpigmentation and fading of existing naevi, have also been reported. In addition, some patients receiving these therapies have developed second primary melanomas. As a consequence, the importance of sequential digital dermoscopy in all patients treated with a BRAFi to detect new primary melanomas has been emphasized. A 61-year-old man with ^V600EBRAF mutant stage IV metastatic melanoma was commenced on the phase 1 trial of LGX818 at 300 mg daily in 2013. After 2 months of therapy, the patient was noted to have developed eruptive naevi, fading of existing naevi and darkening of other naevi. Excision of a new pigmented lesion from the back indicated a compound naevus. Immunohistochemistry showed that the naevus cells lacked a BRAF V600E mutation. This is the first reported case of eruptive naevi in a patient treated with LGX818. The absence of the BRAF V600E mutation within a changing naevus supports the theory that BRAFi stimulates the proliferation of wild-type BRAF cells. Close dermatological surveillance is important for all patients treated with any type of BRAFi.