AACR: Among melanoma patients who were
treated with immunotherapies, those whose tumors had mutations in the
gene NRAS had better response and treatment outcomes than those whose
tumors did not have NRAS mutations, according to a study published in Cancer Immunology Research, a journal of the American Association for Cancer Research.
“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,” 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, tumor 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.
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.