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Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer

In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved “precision” drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line tre...

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Autores principales: Schatz, Stefanie, Falk, Markus, Jóri, Balázs, Ramdani, Hayat O., Schmidt, Stefanie, Willing, Eva-Maria, Menon, Roopika, Groen, Harry J. M., Diehl, Linda, Kröger, Matthias, Wesseler, Claas, Griesinger, Frank, Hoffknecht, Petra, Tiemann, Markus, Heukamp, Lukas C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353063/
https://www.ncbi.nlm.nih.gov/pubmed/32599951
http://dx.doi.org/10.3390/cancers12061685
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author Schatz, Stefanie
Falk, Markus
Jóri, Balázs
Ramdani, Hayat O.
Schmidt, Stefanie
Willing, Eva-Maria
Menon, Roopika
Groen, Harry J. M.
Diehl, Linda
Kröger, Matthias
Wesseler, Claas
Griesinger, Frank
Hoffknecht, Petra
Tiemann, Markus
Heukamp, Lukas C.
author_facet Schatz, Stefanie
Falk, Markus
Jóri, Balázs
Ramdani, Hayat O.
Schmidt, Stefanie
Willing, Eva-Maria
Menon, Roopika
Groen, Harry J. M.
Diehl, Linda
Kröger, Matthias
Wesseler, Claas
Griesinger, Frank
Hoffknecht, Petra
Tiemann, Markus
Heukamp, Lukas C.
author_sort Schatz, Stefanie
collection PubMed
description In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved “precision” drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies. Since PD-L1-negative or low-expressing tumors may also respond to ICI, additional factors are likely to contribute in addition to PD-L1 expression. Tumor mutation burden (TMB) has emerged as a potential candidate; however, it is the most complex biomarker so far and might represent a challenge for routine diagnostics. We therefore established a hybrid capture (HC) next-generation sequencing (NGS) assay that covers all oncogenic driver alterations as well as TMB and validated TMB values by correlation with the assay (F1CDx) used for the CheckMate 227 study. Results of the first consecutive 417 patients analyzed in a routine clinical setting are presented. Data show that fast reliable comprehensive diagnostics including TMB and targetable alterations are obtained with a short turn-around time. Thus, even complex biomarkers can easily be implemented in routine practice to optimize treatment decisions for advanced NSCLC.
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spelling pubmed-73530632020-07-15 Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer Schatz, Stefanie Falk, Markus Jóri, Balázs Ramdani, Hayat O. Schmidt, Stefanie Willing, Eva-Maria Menon, Roopika Groen, Harry J. M. Diehl, Linda Kröger, Matthias Wesseler, Claas Griesinger, Frank Hoffknecht, Petra Tiemann, Markus Heukamp, Lukas C. Cancers (Basel) Article In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved “precision” drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies. Since PD-L1-negative or low-expressing tumors may also respond to ICI, additional factors are likely to contribute in addition to PD-L1 expression. Tumor mutation burden (TMB) has emerged as a potential candidate; however, it is the most complex biomarker so far and might represent a challenge for routine diagnostics. We therefore established a hybrid capture (HC) next-generation sequencing (NGS) assay that covers all oncogenic driver alterations as well as TMB and validated TMB values by correlation with the assay (F1CDx) used for the CheckMate 227 study. Results of the first consecutive 417 patients analyzed in a routine clinical setting are presented. Data show that fast reliable comprehensive diagnostics including TMB and targetable alterations are obtained with a short turn-around time. Thus, even complex biomarkers can easily be implemented in routine practice to optimize treatment decisions for advanced NSCLC. MDPI 2020-06-24 /pmc/articles/PMC7353063/ /pubmed/32599951 http://dx.doi.org/10.3390/cancers12061685 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schatz, Stefanie
Falk, Markus
Jóri, Balázs
Ramdani, Hayat O.
Schmidt, Stefanie
Willing, Eva-Maria
Menon, Roopika
Groen, Harry J. M.
Diehl, Linda
Kröger, Matthias
Wesseler, Claas
Griesinger, Frank
Hoffknecht, Petra
Tiemann, Markus
Heukamp, Lukas C.
Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer
title Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer
title_full Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer
title_fullStr Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer
title_full_unstemmed Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer
title_short Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer
title_sort integration of tumor mutation burden and pd-l1 testing in routine laboratory diagnostics in non-small cell lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353063/
https://www.ncbi.nlm.nih.gov/pubmed/32599951
http://dx.doi.org/10.3390/cancers12061685
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