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Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and
Zachary J Jaeger1, Neel S Raval1, Natalia K A Maverakis2
1Office of Medical Student Education, Washington University School of Medicine, St. Louis, MO, United States.
Introduction:
NRAS mutations are common in melanoma and confer a worse prognosis. Although most patients with metastatic melanoma receive immune checkpoint inhibitors (ICIs), the impact of NRAS mutational status on their efficacy remains under debate.
Methods:
We performed a comprehensive literature search across several large databases. Inclusion criteria were trials, cohorts, and large case series that analyzed the primary outcome of objective response rate by NRAS mutational status in patients with melanoma treated with any line of ICI. At least two reviewers independently screened studies using Covidence software, extracted data, and assessed risk of bias. Standard meta-analysis was performed in R with sensitivity analysis and tests for bias.
Results:
Data on 1770 patients from ten articles were pooled for meta-analysis, and the objective response rate to ICIs was calculated to compare NRAS-mutant and NRAS-wildtype melanoma. The objective response rate was 1.28 (95% confidence interval: 1.01-1.64). Sensitivity analysis identified the study by Dupuis et al. with influential impact on the pooled effect size and heterogeneity, favoring NRAS-mutant melanoma.
Discussion:
In this meta-analysis evaluating the impact of NRAS mutational status on objective response to ICIs in metastatic melanoma, NRAS-mutant cutaneous melanoma demonstrated an increased likelihood of partial or complete tumor response, relative to NRAS-wildtype cutaneous melanoma. Genomic screening for NRAS mutations in patients with metastatic melanoma may improve predictive ability when initiating ICIs.
Insights
NRAS mutations in melanoma patients receiving immune checkpoint inhibitors (ICIs) show a higher response rate. Genomic screening for NRAS mutations may improve treatment prediction for metastatic melanoma.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- NRAS mutations are prevalent in melanoma and associated with poorer prognosis.
- The efficacy of immune checkpoint inhibitors (ICIs) in NRAS-mutant melanoma is debated.
Approach:
- A comprehensive meta-analysis of trials, cohorts, and case series was conducted.
- Data from 1770 patients across ten studies were pooled to compare objective response rates (ORR) in NRAS-mutant versus NRAS-wildtype melanoma treated with ICIs.
- Risk of bias and sensitivity analyses were performed.
Key Points:
- NRAS-mutant melanoma exhibited a significantly increased objective response rate (ORR) to ICIs (ORR 1.28; 95% CI: 1.01-1.64).
- Sensitivity analysis indicated that the Dupuis et al. study had a notable influence on the pooled results, favoring NRAS-mutant melanoma.
- NRAS-mutant cutaneous melanoma showed a greater likelihood of partial or complete tumor response compared to NRAS-wildtype melanoma.
Conclusions:
- NRAS-mutant melanoma patients demonstrate an enhanced response to immune checkpoint inhibitors.
- Genomic assessment for NRAS mutations could refine predictive models for initiating ICI therapy in metastatic melanoma.
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