TY - JOUR
T1 - Mutation-tailored treatment selection in non-small cell lung cancer patients in daily clinical practice
AU - PATH consortium
AU - Steeghs, Elisabeth M.P.
AU - Groen, Harry J.M.
AU - Schuuring, Ed
AU - Aarts, Mieke J.
AU - Damhuis, Ronald A.M.
AU - Voorham, Quirinus J.M.
AU - Ligtenberg, Marjolijn J.L.
AU - Grünberg, Katrien
N1 - Funding Information:
The authors thank Eiko de Jong for his help in the annotation of the pathology data, the Dutch pathology departments that participated in the PATH project, and the registration team of the Netherlands Comprehensive Cancer Organization (IKNL) for the collection of data for the Netherlands Cancer Registry. P. Drillenburg, E.W.P. Nijhuis: Onze Lieve Vrouwe Gasthuis, Amsterdam; M.J. van de Vijver, C.J. van Noesel: Amsterdam UMC, locatie AMC, Amsterdam; E. Bloemena, D.A.M. Heideman, T. Radonic, E: Amsterdam UMC, locatie VUmc, Amsterdam; P.M. Nederlof, G.A. Meijer, K. Monkhorst: Antoni van Leeuwenhoek, Amsterdam; H. Doornewaard: Gelre ziekenhuis, Apeldoorn; M.C.R.F. van Dijk, E. Ruijter: Rijnstate, Arnhem; K. Duthoi: Pathologisch en Cytologisch Laboratorium Amphia, Breda; C. Meijers: Reinier de Graaf Arash, Delft; A.J.C. van de Brule, P.T.G.A. Nooijen: Jeroen Bosch Ziekenhuis, Den Bosch; F.J. Bot: Hagaziekenhuis, Den Haag; H.M. Hazalbag, P. Clahsen: Medisch Centrum Haaglanden/ Bronovo, Den Haag; F.H. van Nederveen, P.J. Westenend: Laboratorium voor Pathologie, Dordrecht; J.W.M. Jeuken: Stichting PAMM, Eindhoven; E.J.M. Ahsmann, P. Meulbroek: Groene Hart Ziekenhuis, Gouda; W. Timens, S.M. Willems, L.C. van Kempen: Universitair Medisch Centrum Groningen, Groningen; W. Geuken: Martini Ziekenhuis, Groningen; N.W.J. Bulkmans, F.E. Bellot: Spaarne Gasthuis, Haarlem; R. Clarijs: Zuyderland Medisch centrum, Sittard-Geleen; S. Riemersma, R. van der Geize: Laboratorium Pathologie Oost Nederland, Hengelo; J. Meijer, H.J. van Slooten: PALGA, Houten; R.E. Kibbelaar, E.M.J. van der Logt: Pathologie Friesland, Leeuwarden; T. van Wezel, D. Cohen: Leids Universitair Medisch Centrum, Leiden; A. Zur Hausen, E.J.M. Speel: Maastricht Universitair Medisch Centrum, Maastricht; P.C. de Bruin, C.J. Huijsmans: St. Antonius Ziekenhuis, Nieuwegein; S. Dusseljee, R.W. Willems, E.K. de Jong: Radboud universitair medisch centrum, Nijmegen; C.F. Prinsen, S. Zomer: Canisius-Wilhelmina Ziekenhuis, Nijmegen; F.J. van Kemenade, W.N.M. Dinjens, W.R.R. Geurts-Giele: Erasmus MC, Rotterdam; H. van der Valk, A.J.J. Smits, K.J. Hoogduin: Pathan BV, Rotterdam; M. Kliffen, M.A. den Bakker: Maasstad ziekenhuis, Rotterdam; J. Stavast: Elisabeth ziekenhuis, Tilburg; P.J. van Diest, W.W.J. de Leng: Universitair Medisch Centrum Utrecht, Utrecht; A.P. de Bru?ne: VieCuri Medisch Centrum, Venlo; J.W.J. Hinrichs, C. Meischl: Symbiant BV, Alkmaar/Hoorn/Den Helder/Zaandam; J. Gaal, M. Niemantsverdriet: Isala, Zwolle.
Funding Information:
The authors declare that they have no conflict of interest. Outside the submitted work MJLL has relationships with AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Merck Sharp & Dohme, Nimagen, Novartis and Roche. KG is a scientific advisor to Bayer, Roche, Bristol-Myers Squibb, AstraZeneca, Roche and Amgen and is responsible for collaborations with Bristol-Myers Squibb, Milestone, Sakura, Illumina; all payments made to Radboudumc. Outside the submitted work MJA has received a research grant from Amgen (paid to the institution). E.S. has performed lectures for Bio-Rad, Novartis, Lilly, Illumina and Agena Bioscience, is scientific advisor for AstraZeneca, Roche, Janssen Pharmaceuticals, Lilly, Pfizer, Novartis, Bayer, BMS, Amgen, BioCartis, Illumina, Agena Bioscience and MSD/Merck, and received research grants from Biocartis, Agena Bioscience, Invitae/Archer, AstraZeneca, Bio-Rad, Roche and Boehringer Ingelheim (all paid to UMCG). HG is scientific advisor for Lilly, Novartis, Roche, Astra-Zeneca and Bristol-Myers Squibb.
Funding Information:
This work was supported by the research program Personalised Medicine of the Netherlands Organization for Health research and Development (ZonMw, project number 846001001).
Publisher Copyright:
© 2022 The Authors
PY - 2022/5
Y1 - 2022/5
N2 - Objectives: The number of targeted drugs in non-small cell lung cancer (NSCLC) is ever-expanding and requires testing of an increasing number of predictive biomarkers. We present a comprehensive real-world evaluation of molecular testing and treatment selection in stage IV NSCLC patients in the Netherlands from 2017 to 2019.Materials and methods: Molecular pathology reports of NSCLC patients were collected from the Dutch Pathology Registry in time intervals between Oct-2017 and April-2019 (N = 5,038 patients) to study diagnostic yield. Linkage between the Dutch Pathology Registry and the Netherlands Cancer Registry enabled studying molecular testing rates for stage IV NSCLC initially diagnosed in 2017-Q4 (N = 1,193) and application of targeted therapy in stage IV NSCLC patients with potentially druggable alterations reported between Oct-2017 and June-2018 (N = 401).Results: Predictive molecular testing was performed in 85.0% of adenocarcinomas, 60.4% of NSCLC-not otherwise specified (NOS) and 17.4% of squamous cell carcinomas. Testing rates were highest for EGFR and ALK (adenocarcinoma: 82.7% and 80.7%, respectively). Incidence of molecular driver alterations (i.e. EGFR, KRAS, ALK, ROS1, BRAF, MET, ERBB2, FGFR1) was 61.1% for adenocarcinomas, 42.3% for NSCLC-NOS, and 24.7% for squamous cell carcinomas. Therapeutically relevant alterations were detected at a higher frequency by NGS- versus non-NGS-approaches (adenocarcinoma: 62.4% versus 56.5%, respectively (P = 0.004)) due to a lower failure rate, more comprehensive testing and higher sensitivity. Uptake of treatment with a registered targeted therapy in eligible patients varied per actionable target, i.e. EGFR: 85.8%, ALK: 74.7%, ROS1: 33.7%, BRAF: 51.5%. Treatment with agents in clinical studies/compassionate use was lower, i.e. MET: 22.8%, HER2: 18.9%, RET: 6.7%.Conclusion: Real-world data show NGS-based approaches to be superior to non-NGS. Uptake of molecular testing and the corresponding targeted treatments was less than expected based on guidelines and even more so for trials, off-label use and compassionate use, indicating less than optimal access to rational treatment options.
AB - Objectives: The number of targeted drugs in non-small cell lung cancer (NSCLC) is ever-expanding and requires testing of an increasing number of predictive biomarkers. We present a comprehensive real-world evaluation of molecular testing and treatment selection in stage IV NSCLC patients in the Netherlands from 2017 to 2019.Materials and methods: Molecular pathology reports of NSCLC patients were collected from the Dutch Pathology Registry in time intervals between Oct-2017 and April-2019 (N = 5,038 patients) to study diagnostic yield. Linkage between the Dutch Pathology Registry and the Netherlands Cancer Registry enabled studying molecular testing rates for stage IV NSCLC initially diagnosed in 2017-Q4 (N = 1,193) and application of targeted therapy in stage IV NSCLC patients with potentially druggable alterations reported between Oct-2017 and June-2018 (N = 401).Results: Predictive molecular testing was performed in 85.0% of adenocarcinomas, 60.4% of NSCLC-not otherwise specified (NOS) and 17.4% of squamous cell carcinomas. Testing rates were highest for EGFR and ALK (adenocarcinoma: 82.7% and 80.7%, respectively). Incidence of molecular driver alterations (i.e. EGFR, KRAS, ALK, ROS1, BRAF, MET, ERBB2, FGFR1) was 61.1% for adenocarcinomas, 42.3% for NSCLC-NOS, and 24.7% for squamous cell carcinomas. Therapeutically relevant alterations were detected at a higher frequency by NGS- versus non-NGS-approaches (adenocarcinoma: 62.4% versus 56.5%, respectively (P = 0.004)) due to a lower failure rate, more comprehensive testing and higher sensitivity. Uptake of treatment with a registered targeted therapy in eligible patients varied per actionable target, i.e. EGFR: 85.8%, ALK: 74.7%, ROS1: 33.7%, BRAF: 51.5%. Treatment with agents in clinical studies/compassionate use was lower, i.e. MET: 22.8%, HER2: 18.9%, RET: 6.7%.Conclusion: Real-world data show NGS-based approaches to be superior to non-NGS. Uptake of molecular testing and the corresponding targeted treatments was less than expected based on guidelines and even more so for trials, off-label use and compassionate use, indicating less than optimal access to rational treatment options.
KW - Adenocarcinoma
KW - Carcinoma, Non-Small-Cell Lung/drug therapy
KW - Carcinoma, Squamous Cell
KW - ErbB Receptors/genetics
KW - Humans
KW - Lung Neoplasms/drug therapy
KW - Mutation/genetics
KW - Protein-Tyrosine Kinases
KW - Proto-Oncogene Proteins/therapeutic use
KW - Proto-Oncogene Proteins B-raf
U2 - 10.1016/j.lungcan.2022.04.001
DO - 10.1016/j.lungcan.2022.04.001
M3 - Article
C2 - 35461050
AN - SCOPUS:85128588907
SN - 0169-5002
VL - 167
SP - 87
EP - 97
JO - Lung Cancer
JF - Lung Cancer
ER -