Journal
CANCER IMMUNOLOGY RESEARCH
Volume 3, Issue 3, Pages 288-295Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-14-0207
Keywords
-
Categories
Funding
- NIH [K12 CA0906525, K24]
- Damon Runyon Clinical Investigator Award
- American Cancer Society Professorship
- Ingram Professorship
- CTSA from the National Center for Advancing Translational Sciences [UL1TR000445]
- Anbinder Fund
Ask authors/readers for more resources
Activating NRAS mutations are found in 15% to 20% of melanomas. Immune therapies have become a mainstay in advanced melanoma treatment. We sought to evaluate whether tumor genotype (e.g., NRAS mutations) correlates with benefit from immune therapy in melanoma. We identified 229 patients with melanoma treated with immune therapies [IL2, ipilimumab, or anti-programmed cell death-1/ligand-1 (PD-1/PD-L1)] at three centers and compared clinical outcomes following immune therapy for patients with or without NRAS mutations. Of the 229 patients with melanoma, 60 had NRAS mutation, 53 had BRAF mutation, and 116 had NRAS/BRAF wild type. The NRAS-mutant cohort had superior or a trend to superior outcomes compared with the other cohorts in terms of response to first-line immune therapy (28% vs. 16%, P = 0.04), response to any line of immune therapy (32% vs. 20%, P = 0.07), clinical benefit (response + stable disease lasting >= 24 weeks; 50% vs. 31%, P < 0.01), and progression-free survival (median, 4.1 vs. 2.9 months, P = 0.09). Benefit from anti-PD-1/PD-L1 was particularly marked in the NRAS cohort (clinical benefit rate 73% vs. 35%). In an independent group of patient samples, NRAS-mutant melanoma had higher PD-L1 expression (although not statistically significant) compared with other genotypes (8/12 vs. 9/20 samples with >= 1% expression; 6/12 vs. 6/20 samples with >= 5% expression), suggesting a potential mechanism for the clinical results. This retrospective study suggests that NRAS mutations in advanced melanoma correlate with increased benefit from immune-based therapies compared with other genetic subtypes. If confirmed by prospective studies, this may be explained in part by high rates of PD-L1 expression. (C) 2015 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available