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Updated: Jul 2, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Clinical Value of Timely Targeted Therapy for Patients With Advanced Non-Small Cell Lung Cancer With Actionable
Thomas Stricker1,2, Neha Jain2, Esprit Ma3
1Tennessee Oncology, Nashville, TN, USA.
Background:
A recent real-world study observed that 24% of patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADOs) initiated nontargeted therapies before biomarker test results became available. This study assessed the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in aNSCLC.
Materials And Methods:
This retrospective analysis of a nationwide electronic health record-derived deidentified database included patients aged ≥18 years diagnosed with aNSCLC with ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, and NTRK) from January 1, 2015, to October 18, 2022, by biomarker testing within 90 days after advanced diagnosis and received 1L treatment. Cohorts were defined by treatment patterns ≤42 days after test results: "Upfront TT" received 1L TT ≤42 days; "Switchers" initiated 1L non-TT before or after testing but switched to TT ≤42 days; and "Non-switchers" initiated non-TT before or after testing and did not switch at any time. Adjusted multivariate Cox regression evaluated real-world progression-free survival, real-world time to next treatment or death, and real-world overall survival.
Results:
A total of 3540 patients met the study criteria; 78% were treated in a community setting, and 50% underwent next-generation sequencing (NGS). There was no significant difference in outcomes between Switchers and Upfront TT; inferior outcomes were observed in Non-switchers versus Upfront TT.
Conclusion:
Our findings demonstrated improved outcomes with upfront 1L TT versus non-TT in patients with aNSCLC with ADOs and observed timely switching to TT after biomarker test result had similar outcomes to Upfront TT. Opportunities remain to improve the use of NGS for early ADO identification and determination of 1L TT.
Insights
Starting targeted therapies upfront or switching to them promptly after biomarker testing improves outcomes for advanced non-small cell lung cancer (aNSCLC) patients with actionable driver oncogenes (ADOs). Delays in treatment or non-targeted therapies lead to worse results.
Area of Science:
- Oncology
- Genomics
- Clinical Research
Background:
- A significant percentage of advanced non-small cell lung cancer (aNSCLC) patients with actionable driver oncogenes (ADOs) receive non-targeted therapies before biomarker test results are available.
- This highlights a critical gap in timely, personalized treatment initiation for aNSCLC.
Purpose of the Study:
- To assess the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in patients with aNSCLC and ADOs.
- To compare outcomes between different treatment initiation strategies based on biomarker testing results.
Main Methods:
- Retrospective analysis of a deidentified electronic health record database (January 2015–October 2022).
- Included patients (≥18 years) with aNSCLC and ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, NTRK), tested within 90 days of diagnosis.
- Cohorts: 'Upfront TT' (≤42 days post-test), 'Switchers' (non-TT then TT ≤42 days post-test), 'Non-switchers' (non-TT only).
Main Results:
- 3540 patients analyzed; 78% treated in community settings, 50% received next-generation sequencing (NGS).
- No significant difference in outcomes between 'Switchers' and 'Upfront TT' cohorts.
- Inferior outcomes observed in 'Non-switchers' compared to 'Upfront TT'.
Conclusions:
- Upfront 1L TT demonstrates improved outcomes compared to non-TT in aNSCLC patients with ADOs.
- Timely switching to TT post-biomarker results yields similar outcomes to upfront TT.
- Opportunities exist to enhance NGS utilization for early ADO identification and guide 1L TT selection.
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