The Influence of c-Kit and NRAS Mutation on Patients’ Survival in Metastatic Melanoma Receiving Immune Checkpoint Inhibitors and Chemotherapy

Abstract

The high metastasis and mortality rates of melanoma in the era of chemotherapy have decreased significantly over the last 10 years. The success is owed largely to the introduction of targeted therapy of oncogenes and immunotherapies, such as checkpoint inhibitors. The aim of the present retrospective, monocentric study is to investigate the impact of chemotherapy or immunotherapy in 550 patients with metastatic melanoma between the years of 2010 and 2019, looking at overall survival while considering BRAF/NRAS/c-KIT mutation status. A total of 17 patients were found to have a c-KIT mutation in exon 11, 13 or 17, including 58.3% with acral lentiginous melanoma, with 53% localized primarily in the lower limbs. In 13.3% of the 231 NRAS-mutated melanomas, primary tumor location was found to be in UV-exposed skin such as on the head and neck, thus about 50% lower than in the 302 patients with wild-type (BRAF-/NRAS-/cKIT-negative) melanoma. Patients with NRAS-mutated melanomas had a significantly lower probability of survival compared to patients with wild-type melanomas, irrespective of the recommendations of the clinical guideline on drug therapy for metastatic melanoma that have been in force since 2010. In contrast to patients with wild-type melanoma who showed a higher probability of survival receiving immune checkpoint inhibitors, the overall survival of patients with NRAS-mutated metastatic melanoma was not more favorable after therapy with immune checkpoint inhibitors compared to chemotherapy treatment.