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Updated: Sep 26, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Mutation-tailored treatment selection in non-small cell lung cancer patients in daily clinical practice
Elisabeth M P Steeghs1, Harry J M Groen2, Ed Schuuring3
1Department of Pathology, Radboudumc, Nijmegen, the Netherlands; Department of Pathology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, the Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
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.
Insights
Molecular testing for non-small cell lung cancer (NSCLC) is crucial for targeted therapies. Real-world data show Next-Generation Sequencing (NGS) is superior, but treatment uptake remains suboptimal.
Area of Science:
- Oncology
- Molecular Pathology
- Pharmacogenomics
Background:
- The increasing number of targeted therapies for non-small cell lung cancer (NSCLC) necessitates comprehensive predictive biomarker testing.
- Real-world evaluation of molecular testing and treatment selection is essential to understand current practices and identify gaps in care for stage IV NSCLC patients.
Purpose of the Study:
- To conduct a comprehensive real-world evaluation of molecular testing and targeted therapy selection in stage IV NSCLC patients in the Netherlands.
- To assess the diagnostic yield of molecular pathology reports and compare the effectiveness of Next-Generation Sequencing (NGS) versus non-NGS approaches.
- To determine the uptake of targeted therapies and identify barriers to accessing rational treatment options.
Main Methods:
- Molecular pathology reports (N=5,038) from Oct-2017 to April-2019 were collected from the Dutch Pathology Registry.
- Linkage with the Netherlands Cancer Registry allowed analysis of molecular testing rates (N=1,193) and targeted therapy application (N=401) in stage IV NSCLC.
- Comparison of NGS and non-NGS approaches for detecting therapeutically relevant alterations.
Main Results:
- Predictive molecular testing was performed in 85.0% of adenocarcinomas, 60.4% of NSCLC-NOS, and 17.4% of squamous cell carcinomas.
- Next-Generation Sequencing (NGS) detected therapeutically relevant alterations more frequently than non-NGS approaches (62.4% vs. 56.5%, P=0.004).
- Uptake of registered targeted therapies varied by actionable target (EGFR: 85.8%, ALK: 74.7%), with lower uptake for clinical trials or compassionate use.
Conclusions:
- Real-world data confirm the superiority of NGS-based approaches for molecular testing in NSCLC.
- The uptake of molecular testing and targeted treatments is lower than anticipated based on guidelines.
- There is suboptimal access to rational treatment options, including clinical trials and off-label use, indicating a need for improved patient access.
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