The evolving landscape of biomarker testing for non-small cell lung cancer in Europe. (April 2021)

• Record Type: Journal Article
• Authors: Kerr, Keith M.; Bibeau, Frédéric; Thunnissen, Erik; Botling, Johan; Ryška, Aleš; Wolf, Jürgen; Öhrling, Katarina; Burdon, Peter; Malapelle, Umberto; Büttner, Reinhard
• Is Part Of: Lung cancer. Volume 154(2021)
• Page Start: 161
• Page End: 175
• Publication Date: 2021-04
• Subjects: ALK anaplastic lymphoma kinase -- AMP Association for Molecular Pathology -- ASCO American Society of Clinical Oncology -- BRAF B-Raf proto-oncogene -- CAP College of American Pathologists -- ctDNA circulating tumour cell DNA -- ddPCR digital droplet PCR -- EGFR epidermal growth factor receptor -- EMQN European Molecular Genetics Quality Network -- EQA external quality assessment -- ERBB2 Erb-B2 receptor tyrosine kinase 2 -- ESCAT ESMO Scale of Clinical Actionability of Molecular Targets -- ESMO European Society for Medical Oncology -- FDA Food and Drug Administration -- FGFR fibroblast growth factor receptor -- FISH fluorescence in situ hybridisation -- FNA fine needle aspiration -- HER human epidermal growth factor receptor -- IASLC International Association for the Study of Lung Cancer -- ICC immunocytochemistry -- IHC immunohistochemistry -- ISH in situ hybridisation -- KRAS Kirsten rat sarcoma viral oncogene homolog -- MEK mitogen-activated protein kinase kinase -- MET hepatocyte growth factor receptor -- MTB molecular tumour board -- NCCN National Comprehensive Cancer Network -- NEQAS National External Quality Assessment Service -- NGS next-generation sequencing -- NRG1 neuregulin-1 -- NSCLC non-small cell lung cancer -- NTRK neurotrophic tyrosine receptor kinase -- OncoKB Oncology Knowledge Base -- PCR polymerase chain reaction -- PD-1 programmed cell death protein 1 -- PD-L1 programmed cell death protein ligand 1 -- qPCR quantitative PCR -- QuIP Quality Initiative for Pathology -- RET rearranged during transfection -- ROS1 ROS proto-oncogene 1 -- ROSE rapid on-site evaluation -- RT-PCR real-time polymerase chain reaction -- SGT single-gene testing -- SOC standard of care -- SOP standard operating procedures -- TAT turnaround time -- TMB tumour mutational burden -- VAF variant allele frequency; Precision medicine -- Predictive molecular pathology -- Targeted therapies -- Next-generation sequencing -- Oncogenic driver mutations -- NSCLC; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2021.02.026
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Molecular testing determines appropriate targeted therapies for advanced NSCLC. Country-specific differences exist in molecular testing availability across Europe. Molecular tumour board and reflex molecular testing strategies are desirable. Next-generation sequencing permits comprehensive molecular testing. Cell-free DNA-based analysis facilitates re-testing to guide subsequent treatment. Abstract: The discovery of oncogenic driver mutations rendering non-small cell lung cancer (NSCLC) targetable by small-molecule inhibitors, and the development of immunotherapies, have revolutionised NSCLC treatment. Today, instead of non-selective chemotherapies, all patients with advanced NSCLC eligible for treatment (and increasing numbers with earlier, less extensive disease) require fast and comprehensive screening of biomarkers for first-line patient selection for targeted therapy, chemotherapy, or immunotherapy (with or without chemotherapy). To avoid unnecessary re-biopsies, biomarker screening before first-line treatment should also include markers that are actionable from second-line onwards; PD-L1 expression testing is also mandatory before initiating treatment. Population differences exist in the frequency of oncogenic driver mutations: EGFR mutations are more frequent in Asia than Europe, whereas the converse is true for KRAS mutations. In addition to approved first-line therapies, a number of emerging therapies are being investigated in clinical trials. Guidelines for biomarker testing vary by country, with the number of actionable targets and the requirement for extensive molecular screening strategies expected to increase. To meet diagnostic demands, rapid screening technologies for single-driver mutations have been implemented. Improvements in DNA- and RNA-based next-generation sequencing technologies enable analysis of a group of genes in one assay; however, turnaround times remain relatively long. Consequently, rapid screening technologies are being implemented alongside next-generation sequencing. Further challenges in the evolving landscape of biomarker testing in NSCLC are actionable primary and secondary resistance mechanisms to targeted therapies. Therefore, comprehensive testing on re-biopsies, collected at the time of disease progression, in combination with testing of circulating tumour DNA may provide important information to guide second- or third-line therapies. Furthermore, longitudinal biomarker testing can provide insights into tumour evolution and heterogeneity during the course of the disease. We summarise best practice strategies for Europe in the changing landscape of biomarker testing at diagnosis and during treatment.