Among melanoma patients who were treated with immunotherapies, those whose tumours had mutations in the gene NRAS had better response and treatment outcomes than those whose tumours did not have NRAS mutations, according to a study published in Cancer Immunology Research.

“In a retrospective study, we found that patients with NRAS-mutant melanoma seemed to respond better to immunotherapy compared with patients whose tumours had other genetic subtypes, and this was especially true for patients treated with anti-PD-1/PD-L1 therapies,” said Douglas B. Johnson, MD, an assistant professor of medicine at Vanderbilt-Ingram Cancer Center (VICC) in Nashville, Tennessee.

“We studied a small group of patients, but the results were quite suggestive. Our findings need to be confirmed in a prospective study.”

Johnson and colleagues found that 28 percent of the patients with NRAS-mutant melanoma had complete or partial responses with first-line immunotherapy 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 immunotherapy ipilimumab as well.

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

“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.”

Johnson and colleagues used electronic medical records of 229 melanoma patients treated at VICC, Memorial Sloan Kettering Cancer Center, 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, compared with patients whose tumors had the normal form of NRAS, those with NRAS mutations had slightly higher levels of the PD-L1 protein—a protein which, in some cases, correlates with response to anti-PD-1/PD-L1 drugs.

Reference

Johnson1, Lovly,  Flavin et al., Impact of NRAS mutations for patients with advanced melanoma treated with immune therapies, Cancer Immunology Research

Source: AACR