Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783557787628863488 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7353063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT schatzstefanie integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT falkmarkus integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT joribalazs integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT ramdanihayato integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT schmidtstefanie integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT willingevamaria integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT menonroopika integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT groenharryjm integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT diehllinda integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT krogermatthias integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT wesselerclaas integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT griesingerfrank integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT hoffknechtpetra integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT tiemannmarkus integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer AT heukamplukasc integrationoftumormutationburdenandpdl1testinginroutinelaboratorydiagnosticsinnonsmallcelllungcancer |