encorafenib and Nevus--Pigmented

Topics: Carbamates; Cetuximab; Humans; Nevus, Pigmented; Skin Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Carbamates; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Humans; Nevus, Pigmented; Proto-Oncogene Proteins B-raf; Sulfonamides

Encorafenib is a BRAF inhibitor increasingly used as a second-line treatment for metastatic melanoma and colorectal cancer. BRAF inhibitors have been reported to be associated with new and changing melanocytic lesions, including eruptive naevi. We describe two cases of eruptive naevi secondary to encorafenib used for the treatment of BRAF-mutant metastatic colorectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carbamates; Colonic Neoplasms; Exanthema; Humans; Mutation; Nevus, Pigmented; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Rectal Neoplasms; Skin Neoplasms; Sulfonamides

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 BRAF 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.

Topics: Antineoplastic Agents; Carbamates; Dermatology; Dermoscopy; Humans; Male; Melanoma; Middle Aged; Mutation; Neoplasm Metastasis; Nevus, Pigmented; Pigmentation; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Sulfonamides