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Correlation of KRAS G12C Mutation and High PD-L1 Expression with Clinical Outcome in NSCLC Patients Treated with Anti-PD1 Immunotherapy

Background: Immune checkpoint inhibitors (ICIs) targeting PD-1 or PD-L1 improved the survival of non-small cell lung cancer (NSCLC) patients with PD-L1 expression ≥50% and without alterations in EGFR, ALK, ROS1, RET. However, markers able to predict the efficacy of ICIs, in combination with PD-L1 ex...

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Autores principales: Cefalì, Marco, Epistolio, Samantha, Ramelli, Giulia, Mangan, Dylan, Molinari, Francesca, Martin, Vittoria, Freguia, Stefania, Mazzucchelli, Luca, Froesch, Patrizia, Frattini, Milo, Wannesson, Luciano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954500/
https://www.ncbi.nlm.nih.gov/pubmed/35329953
http://dx.doi.org/10.3390/jcm11061627
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author Cefalì, Marco
Epistolio, Samantha
Ramelli, Giulia
Mangan, Dylan
Molinari, Francesca
Martin, Vittoria
Freguia, Stefania
Mazzucchelli, Luca
Froesch, Patrizia
Frattini, Milo
Wannesson, Luciano
author_facet Cefalì, Marco
Epistolio, Samantha
Ramelli, Giulia
Mangan, Dylan
Molinari, Francesca
Martin, Vittoria
Freguia, Stefania
Mazzucchelli, Luca
Froesch, Patrizia
Frattini, Milo
Wannesson, Luciano
author_sort Cefalì, Marco
collection PubMed
description Background: Immune checkpoint inhibitors (ICIs) targeting PD-1 or PD-L1 improved the survival of non-small cell lung cancer (NSCLC) patients with PD-L1 expression ≥50% and without alterations in EGFR, ALK, ROS1, RET. However, markers able to predict the efficacy of ICIs, in combination with PD-L1 expression are still lacking. Our aim in this hypothesis-generating pilot study was to evaluate whether the KRAS G12C variant may predict the efficacy of ICIs in advanced NSCLC patients with PD-L1 ≥ 50%. Methods: Genomic DNA or tissue sections of 44 advanced ICI-treated NSCLC cases with PD-L1 ≥ 50% without EGFR, ALK, ROS1, RET alterations were tested using Next Generation Sequencing, Fluorescence in Situ Hybridization and immunohistochemistry. Statistical analyses were carried out fitting univariate and multivariate time to event models. Results: KRAS G12C mutant patients (N = 11/44) showed a significantly longer progression-free survival (PFS) at univariate and multivariate analyses (p = 0.03). The Kaplan–Meier plot of the PFS time-to-event supports that G12C positive patients have a longer time to progress. PFS improvement was not observed when any KRAS mutations were compared to wild-type cases. Conclusions: Given the limitations due to the small sample size and exploratory nature of this study, we tentatively conclude the KRAS G12C mutation should be considered in future trials as a predictive marker of prolonged response to first-line ICIs in NSCLC patients overexpressing PD-L1. This finding could be relevant as anti-KRAS G12C therapies enter the therapeutic landscape of NSCLC.
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spelling pubmed-89545002022-03-26 Correlation of KRAS G12C Mutation and High PD-L1 Expression with Clinical Outcome in NSCLC Patients Treated with Anti-PD1 Immunotherapy Cefalì, Marco Epistolio, Samantha Ramelli, Giulia Mangan, Dylan Molinari, Francesca Martin, Vittoria Freguia, Stefania Mazzucchelli, Luca Froesch, Patrizia Frattini, Milo Wannesson, Luciano J Clin Med Article Background: Immune checkpoint inhibitors (ICIs) targeting PD-1 or PD-L1 improved the survival of non-small cell lung cancer (NSCLC) patients with PD-L1 expression ≥50% and without alterations in EGFR, ALK, ROS1, RET. However, markers able to predict the efficacy of ICIs, in combination with PD-L1 expression are still lacking. Our aim in this hypothesis-generating pilot study was to evaluate whether the KRAS G12C variant may predict the efficacy of ICIs in advanced NSCLC patients with PD-L1 ≥ 50%. Methods: Genomic DNA or tissue sections of 44 advanced ICI-treated NSCLC cases with PD-L1 ≥ 50% without EGFR, ALK, ROS1, RET alterations were tested using Next Generation Sequencing, Fluorescence in Situ Hybridization and immunohistochemistry. Statistical analyses were carried out fitting univariate and multivariate time to event models. Results: KRAS G12C mutant patients (N = 11/44) showed a significantly longer progression-free survival (PFS) at univariate and multivariate analyses (p = 0.03). The Kaplan–Meier plot of the PFS time-to-event supports that G12C positive patients have a longer time to progress. PFS improvement was not observed when any KRAS mutations were compared to wild-type cases. Conclusions: Given the limitations due to the small sample size and exploratory nature of this study, we tentatively conclude the KRAS G12C mutation should be considered in future trials as a predictive marker of prolonged response to first-line ICIs in NSCLC patients overexpressing PD-L1. This finding could be relevant as anti-KRAS G12C therapies enter the therapeutic landscape of NSCLC. MDPI 2022-03-15 /pmc/articles/PMC8954500/ /pubmed/35329953 http://dx.doi.org/10.3390/jcm11061627 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cefalì, Marco
Epistolio, Samantha
Ramelli, Giulia
Mangan, Dylan
Molinari, Francesca
Martin, Vittoria
Freguia, Stefania
Mazzucchelli, Luca
Froesch, Patrizia
Frattini, Milo
Wannesson, Luciano
Correlation of KRAS G12C Mutation and High PD-L1 Expression with Clinical Outcome in NSCLC Patients Treated with Anti-PD1 Immunotherapy
title Correlation of KRAS G12C Mutation and High PD-L1 Expression with Clinical Outcome in NSCLC Patients Treated with Anti-PD1 Immunotherapy
title_full Correlation of KRAS G12C Mutation and High PD-L1 Expression with Clinical Outcome in NSCLC Patients Treated with Anti-PD1 Immunotherapy
title_fullStr Correlation of KRAS G12C Mutation and High PD-L1 Expression with Clinical Outcome in NSCLC Patients Treated with Anti-PD1 Immunotherapy
title_full_unstemmed Correlation of KRAS G12C Mutation and High PD-L1 Expression with Clinical Outcome in NSCLC Patients Treated with Anti-PD1 Immunotherapy
title_short Correlation of KRAS G12C Mutation and High PD-L1 Expression with Clinical Outcome in NSCLC Patients Treated with Anti-PD1 Immunotherapy
title_sort correlation of kras g12c mutation and high pd-l1 expression with clinical outcome in nsclc patients treated with anti-pd1 immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954500/
https://www.ncbi.nlm.nih.gov/pubmed/35329953
http://dx.doi.org/10.3390/jcm11061627
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