Melanoma Coverage from Every Angle

Responses to Immune Checkpoint Inhibitors in Patients With NRAS-Mutant Melanoma

By: Anna Nowogrodzki
Posted: Wednesday, August 1, 2018

Patients with NRAS-mutant melanoma responded to immune checkpoint inhibition at similar rates to those with NRAS–wild-type melanoma, although their overall survival was lower, according to a retrospective multicenter analysis. The study was published in the European Journal of Cancer by Lucie Heinzerling, MD, MPH, of the University Hospital Erlangen and the University Erlangen-Nürnberg in Germany, and colleagues.

The investigators examined the records of 364 patients with metastatic melanoma from 5 skin cancer centers in Germany and Switzerland: 236 had NRAS mutation(s) and 128 had NRAS–wild-type melanoma. All patients had been treated with either an anti–PD-1 therapy (nivolumab or pembrolizumab), an anti–CTLA-4 therapy (ipilimumab), or both.

The rates of response to therapy were similar for NRAS-mutant patients compared with NRAS–wild-type patients for all therapies: ipilimumab (15% for mutant vs. 13% for wild-type), anti–PD-1 therapy (21% vs. 13%), and ipilimumab plus anti–PD-1 therapy either concurrently or in succession (40% vs. 39%). However, overall survival was worse for patients with NRAS-mutant melanoma: 21 months, compared with 33 months for those with NRAS–wild-type melanoma.

The investigators found a trend toward an overall survival benefit when patients with NRAS-mutant melanoma were treated with oral MEK inhibitors before or after immune checkpoint inhibitor therapy, although it was not statistically significant. Based on this trend, the authors speculate that additional MEK inhibition might improve the clinical benefit of immune checkpoint inhibition.

“The more pronounced clinical benefit of MEK inhibitors after immunotherapy may be attributed to a late benefit of immunotherapy,” the investigators proposed. “But since our study showed that patients with immunotherapy after MEK inhibitor treatment also had better survival, this could be a consequence of immunoediting and changes in the tumour microenvironment by the MEK kinase inhibitor.”

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