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      Future perspective for the application of predictive biomarker testing in advanced stage non-small cell lung cancer

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          Summary

          For patients with advanced stage non-small cell lung cancer (NSCLC), treatment strategies have changed significantly due to the introduction of targeted therapies and immunotherapy. In the last few years, we have seen an explosive growth of newly introduced targeted therapies in oncology and this development is expected to continue in the future. Besides primary targetable aberrations, emerging diagnostic biomarkers also include relevant co-occurring mutations and resistance mechanisms involved in disease progression, that have impact on optimal treatment management. To accommodate testing of pending biomarkers, it is necessary to establish routine large-panel next-generation sequencing (NGS) for all patients with advanced stage NSCLC. For cost-effectiveness and accessibility, it is recommended to implement predictive molecular testing using large-panel NGS in a dedicated, centralized expert laboratory within a regional oncology network. The central molecular testing center should host a regional Molecular Tumor Board and function as a hub for interpretation of rare and complex testing results and clinical decision-making.

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          Most cited references49

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          Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

          NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.
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            Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group

            Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology.
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              Trastuzumab Deruxtecan in HER2-Mutant Non–Small-Cell Lung Cancer

              Human epidermal growth factor receptor 2 (HER2)-targeted therapies have not been approved for patients with non-small-cell lung cancer (NSCLC). The efficacy and safety of trastuzumab deruxtecan (formerly DS-8201), a HER2 antibody-drug conjugate, in patients with HER2-mutant NSCLC have not been investigated extensively.
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                Author and article information

                Contributors
                Journal
                Lancet Reg Health Eur
                Lancet Reg Health Eur
                The Lancet Regional Health - Europe
                Elsevier
                2666-7762
                01 March 2024
                March 2024
                01 March 2024
                : 38
                : 100839
                Affiliations
                [a ]Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
                [b ]Oncostat U1018, Inserm, Paris-Saclay University, Gustave Roussy, Villejuif, France
                [c ]Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy of University of Gothenburg, Gothenburg, Sweden
                [d ]Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria
                [e ]Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany
                [f ]Pulmonology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
                [g ]Charles University and Thomayer Hospital, Prague, Czech Republic
                [h ]Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria
                [i ]Department of Respiratory and Critical Care Medicine, Klinik Floridsdorf, Vienna Healthcare Group, Vienna, Austria
                [j ]IHU RespirERA, FHU OncoAge, Nice University Hospital, Côte d’Azur University, Nice, France
                [k ]Department of Oncology, University Hospital Antwerp, University of Antwerp, Edegem, Belgium
                [l ]Department of Pathology, University Hospital Antwerp, University of Antwerp, Edegem, Belgium
                [m ]Laboratory for Cytology and Pathology, University Clinic Golnik, Golnik, Slovenia
                [n ]Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
                [o ]Faculty of Medicine of the University of Porto, Portugal
                [p ]Institute for Research and Innovation in Health (i3S), Porto, Portugal
                [q ]University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia
                [r ]Lung Unit, Royal Marsden NHS Trust, London, England, UK
                [s ]The Fingerland Department of Pathology, Charles University Medical Faculty and University Hospital, Czech Republic
                [t ]Lung Cancer Group Cologne, Department I for Internal Medicine and Center for Integrated Oncology Cologne/Bonn, University Hospital Cologne, Cologne, Germany
                [u ]Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
                Author notes
                []Corresponding author. a.j.van.der.wekken@ 123456umcg.nl
                [∗∗ ]Corresponding author. e.schuuring@ 123456umcg.nl
                [v]

                These authors contributed equally to this manuscript.

                Article
                S2666-7762(24)00005-X 100839
                10.1016/j.lanepe.2024.100839
                10928270
                38476751
                a12308da-da64-4ac7-875d-78a9adf117ef
                © 2024 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 September 2023
                : 16 November 2023
                : 8 January 2024
                Categories
                Series Viewpoint

                predictive biomarker testing,next-generation sequencing,non-small cell lung cancer

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