NRAS & BRAF Mutational Status May Help Guide Therapy in Melanoma Patients

A new study is suggesting that it may be important to look at mutational status when determining adjuvant treatments for melanoma patients. Researchers at the University of North Carolina (UNC) School of Medicine are now reporting that NRAS and BRAF mutations in melanoma patients should be identified early, and may need to be taken into consideration when establishing treatment paradigms.

The results of this study were published online in the April 9, 2015 issue of JAMA Oncology.

Researchers looked at data from the Genes, Environment, and Melanoma (GEM) Study, which included 912 patients with a median follow-up of 7.6 years. They examined tumor characteristics and melanoma-specific survival of primary melanoma by NRAS and BRAF mutational status.  They found 13% of the patients had tumors with NRAS mutations, 30% had BRAF mutations, and 57% had neither.

There was no statistically significant difference in the 5-year survival rates for patients with NRAS or BRAF-mutated melanoma tumors compared with survival in those patients with tumors lacking mutations. However, there were lower 5-year survival rates for patients with higher-risk tumors with mutations. The study suggested the 5-year survival rate was 73% for patients with high-risk NRAS-mutated tumors, 71% for patients with high-risk tumors with BRAF mutations, and 82% for patients with high-risk cancer and lacking either mutation.

The investigators found there was a lower tumor-infiltrating lymphocyte grade for NRAS-mutated melanoma, suggesting it has a more immunosuppressed microenvironment and may have an altered response to immunotherapy drugs.

Principal study investigator Nancy Thomas, MD, PHD, who is a professor in the UNC School of Medicine Department of Dermatology, said in this patient population, mutational status is associated with lower survival and these new study findings may help inform treatment decisions. Dr. Thomas said many new oral targeted therapies have been shown to be relatively safe and so there may now be new pressure to use these agents earlier as adjuvant treatments. This study suggests certain patients might be at higher risk and may be better candidates for adjuvant treatment. 

Dr. Thomas noted that one of the major findings of this study is that melanomas with a mutation in the NRAS gene have fewer tumor-infiltrating lymphocytes. She said that is important because new immunotherapies often require infiltrating lymphocytes to be present in order for the treatments to work.

Study co-author Kathleen Dorsey, PhD, who is an assistant professor of cancer epidemiology in the UNC School of Medicine, agreed that the findings may have clinical implications for people with the mutations, and higher-risk cancer since the study showed an approximately threefold increased risk of death from NRAS and BRAF mutations that was limited to higher-stage tumors. She said mutational status could also be important for determining eligibility for adjuvant trials.

References:

• UNC Healthcare and UNC School of Medicine: Newsroom. (2015). Lower survival rates connected with high-risk melanoma with mutations, study finds.