Cargando…
Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis
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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9979544/ https://www.ncbi.nlm.nih.gov/pubmed/36873887 http://dx.doi.org/10.3389/fmed.2023.1090737 |
_version_ | 1784899747654402048 |
---|---|
author | Jaeger, Zachary J. Raval, Neel S. Maverakis, Natalia K. A. Chen, David Y. Ansstas, George Hardi, Angela Cornelius, Lynn A. |
author_facet | Jaeger, Zachary J. Raval, Neel S. Maverakis, Natalia K. A. Chen, David Y. Ansstas, George Hardi, Angela Cornelius, Lynn A. |
author_sort | Jaeger, Zachary J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9979544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99795442023-03-03 Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis Jaeger, Zachary J. Raval, Neel S. Maverakis, Natalia K. A. Chen, David Y. Ansstas, George Hardi, Angela Cornelius, Lynn A. Front Med (Lausanne) Medicine 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. Frontiers Media S.A. 2023-02-16 /pmc/articles/PMC9979544/ /pubmed/36873887 http://dx.doi.org/10.3389/fmed.2023.1090737 Text en Copyright © 2023 Jaeger, Raval, Maverakis, Chen, Ansstas, Hardi and Cornelius. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Jaeger, Zachary J. Raval, Neel S. Maverakis, Natalia K. A. Chen, David Y. Ansstas, George Hardi, Angela Cornelius, Lynn A. Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis |
title | Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis |
title_full | Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis |
title_fullStr | Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis |
title_full_unstemmed | Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis |
title_short | Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis |
title_sort | objective response to immune checkpoint inhibitor therapy in nras-mutant melanoma: a systematic review and meta-analysis |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9979544/ https://www.ncbi.nlm.nih.gov/pubmed/36873887 http://dx.doi.org/10.3389/fmed.2023.1090737 |
work_keys_str_mv | AT jaegerzacharyj objectiveresponsetoimmunecheckpointinhibitortherapyinnrasmutantmelanomaasystematicreviewandmetaanalysis AT ravalneels objectiveresponsetoimmunecheckpointinhibitortherapyinnrasmutantmelanomaasystematicreviewandmetaanalysis AT maverakisnataliaka objectiveresponsetoimmunecheckpointinhibitortherapyinnrasmutantmelanomaasystematicreviewandmetaanalysis AT chendavidy objectiveresponsetoimmunecheckpointinhibitortherapyinnrasmutantmelanomaasystematicreviewandmetaanalysis AT ansstasgeorge objectiveresponsetoimmunecheckpointinhibitortherapyinnrasmutantmelanomaasystematicreviewandmetaanalysis AT hardiangela objectiveresponsetoimmunecheckpointinhibitortherapyinnrasmutantmelanomaasystematicreviewandmetaanalysis AT corneliuslynna objectiveresponsetoimmunecheckpointinhibitortherapyinnrasmutantmelanomaasystematicreviewandmetaanalysis |