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Gene alterations in melanoma may predict immunotherapy outcomes

Among who were treated with immunotherapies, those whose tumors had in the gene had better response and treatment outcomes than those whose tumors did not have mutations.

The study is published in Cancer Immunology Research, a journal of the .

Although immunotherapies have become a main treatment option for patients with melanoma, tumor markers that can identify patients who will benefit the most from these therapies is an important step in improving treatment outcomes, Johnson explained.

Johnson and colleagues used electronic medical records of 229 melanoma patients treated at VICC, , and Massachusetts General Hospital. Of the patients, 143 received ipilimumab, 58 received IL-2 therapy, and 28 received anti-PD-1/PD-L1 drugs as first-line therapy.

Sixty patients had tumors with NRAS mutations, 53 had BRAF mutations, and 116 had the normal forms of these two genes.

The researchers found that 28 percent of the patients with NRAS-mutant melanoma had complete or partial responses with first-line compared with 16 percent of those who had the normal form of the gene. The clinical benefit rate (complete or partial response, or stable disease lasting 24 weeks or more) with anti-PD-1/PD-L1 drugs was 73 percent for those with NRAS mutations and 35 percent for those with the normal form of the gene. Patients with NRAS mutations had a trend for better outcome when treated with the ipilimumab as well.

In an interview, Johnson said, “In a retrospective study, we found that patients with NRAS-mutant melanoma seemed to respond better to immunotherapy compared with patients whose tumors had other genetic subtypes, and this was especially true for patients treated with anti-PD-1/PD-L1 therapies. We studied a small group of patients, but the results were quite suggestive. Our findings need to be confirmed in a prospective study. This study highlights the need to find predictive markers that can help us understand which patients will respond to therapy. Our study will hopefully lead to understanding the biological mechanisms that explain why NRAS mutations predict response. We are currently conducting studies to explain this finding.”

This study was funded by the National Institutes of Health, the Damon Runyon Clinical Investigator Award, the American Cancer Society, the Vanderbilt-Ingram Cancer Center, the National Center for Advancing Translational Sciences, the Joyce Family Foundation, the Martell Foundation, the Bradford Family Foundation, and the Anbinder Fund. Johnson declares no conflicts of interest. Study co-author Christine Lovly has research grants from AstraZeneca and Novartis; co-author A. John Iafrate has ownership in ArcherDx and is on the advisory board of BioReference Labs.


Impact of NRAS Mutations for Patients with Advanced Melanoma Treated with Immune Therapies, Douglas B. Johnson, Christine M. Lovly, Marisa Flavin, Katherine S. Panageas, Gregory D. Ayers, Zhiguo Zhao, Wade T. Iams, Marta Colgan, Sarah DeNoble, Charles R. Terry, Elizabeth G. Berry, A. John Iafrate, Ryan J. Sullivan, Richard D. Carvajal, and Jeffrey A. Sosman, Cancer Immunology Research, doi: 10.1158/2326-6066.CIR-14-0207, published March 2015.

Source: American Association for Cancer Research (AACR)