Good news for NRAS positive folks, especially in regard to anti-PD1!!!!

Abstract presented at the American Association for Cancer Research, April 2014

NRAS mutation as a predictor of response to immune-based therapies in patients with metastatic melanoma.  Iams, Johnson, Flavin, Zhao, Sosman, et al.

"Immune based therapies are playing an expanding role in the treatment of advanced melanoma.  Reliable biomarkers to predict benefit from these agents have not yet been identified....  Approximately 15-20% of patients with melanoma harbor an NRAS mutation...  We assessed whether NRAS mutations impact the response to immune-based therapy..."

Examined 171 patients from 3 institutions with advanced melanoma and known tumor genotype.  All were treated with either IL-2, anti-CTLA-4 (ipi/yervoy), or anti-PD1lPD-L1 inhibitors.  "We compared the rates of clinical response between patients with NRAS mutant melanoma and those without NRAS or BRAF mutations (wild type)..." 

End points: CR = Complete Response, PR = partial response.  Secondary end points:  CB = clinical benefit (defined as CR/PR or stable disease for more than 24 weeks), PFS = progression free survival, and OS = overall survival.

59 patients (35%) had NRAS-mutant melanoma.  112 patients (65%) had WT (wild type)... There was a significantly higher rate of CR/PR and CB in patients with NRAS vs  patients with WT melanoma.  (32% vs 18% for CR/PR and 49% vs 29% for CB).  "Within specific immune therapy types, patients with NRAS-mutant melanoma experienced the greatest benefit in CR/PR compared to patients with WT melanoma when treated with anti-PD1/PD-L1 agents (70% vs 20%)."  No statistically significant differences in median PFS or median OS were observed.

Conclusion:  Patients with NRAS mutation experience a higher rate of CR/PR and CB when treated with immune-based therapy vs patients with WT.  Data suggest that routine assessment for NRAS mutations in patients with melanoma is warranted.

A ray of light for folks with NRAS mutation. And maybe one more reason not to make them go through ipi before they get to take anti-PD1???!!!!!  Best - c