Résumé
NRAS mutation, the second main oncodriver in melanoma, is present in 20% of cases and associated with a histologically and clinically more aggressive disease with a poorer prognosis. To date, no targeted therapy specifically acting on NRAS mutation is routinely used and no specific recommendationshave been issued regarding NRAS-mutated melanoma. However, MEK inhibitors as monotherapy or in combination with immunotherapy are increasingly used in practice in advanced NRAS-mutated melanomas, especially in second line. We conducted a retrospective survey of the efficacy and safety of MEK inhibitors as monotherapy or in combination with immunotherapy in patients with advanced stage wild NRAS-mutated BRAF-WT melanomas based on the national MelBase cohort, in second line therapy or beyond. The overall objective response rate was 16.6% and the overall disease control rate was 46.2%. Median overall survival was 7.6 months and median progression-free survival was 2.5 months. We found no statistically significant differences between patients treated with a MEK inhibitor alone or in combination with immunotherapy for both response data and secondary endpoints such as overall survival, progression-free survival, type, duration and timing of response, including for patients with brain metastases. Patients treated with MEK inhibitor alone displayed more frequently unfavorable prognosis criteria such as ECOG status, LDH level and number of metastatic sites, making the study population heterogeneous. The combination with immunotherapy did not increase the overall toxicity. This multicenter “real-life” study including patients with poor prognosis compared the benefit of anti-MEK alone or in combination with immunotherapy but probably lacked statistical power.