A potential role for nilotinib in KIT-mutated melanoma

Introduction: The advent of effective immunotherapy and targeted therapy, such as ipilimumab (anti-CTLA-4 monoclonal antibody) and vemurafenib (BRAF inhibitor), are changing the treatment paradigm for metastatic melanoma. One of the most readily recognized targets in metastatic melanoma is the oncogenic 'driver' mutations KIT, which is thought to be an important driver mutation in up to 3% of melanomas. Areas covered: We review the current state of development of KIT-targeted agents in melanoma with KIT mutations. The pharmacokinetic and pharmacodynamic profiles of nilotinib are presented, as well its safety clinical activity data. Finally, we present the knowledge learned from the experience of nilotinib in chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) to guide its development for melanoma. Expert opinion: Given its favorable safety and efficacy profile in CML and imatinib-resistant GISTs, nilotinib, a second-generation tyrosine kinase inhibitor with greater potency than imatinib, emerges as a promising agent in the treatment of metastatic melanoma harboring the KIT mutation and warrants clinical investigation in this setting.