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Updated: Nov 30, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Long term follow-up of EGFR mutated NSCLC cases
Gad Rennert1, Maya Gottfried2, Hedy S Rennert3
1Clalit Health Services National Cancer Control Center and Personalized Medicine Program, Israel; Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Office of Chief Physician, Clalit Health Services Headquarters, Tel Aviv, Israel.
Purpose:
A substantial fraction of all non-small cell lung cancers(NSCLC) carry a mutation in the EGFR gene for which an effective treatment with anti-tyrosine kinases(TKIs) is available. We studied the long term survival of these patients following the introduction of TKIs.
Experimental Design:
All consecutive cases of NSCLC newly diagnosed with advanced disease were referred for free tumor EGFR mutation testing at Clalit's national personalized medicine laboratory. Mutations and deletions in target codons 18-21 of EGFR were sought using RT-PCR and fragment analysis. Comprehensive EMRs were used to collect full data on treatments and clinical status.
Results:
A cohort of 3,062 advanced NSCLC cases, included 481(15.7%) somatic EGFR mutation carriers (17.5% of all adenocarcinomas, 26.7% of females with adenocarcinomas). TKIs treatment to EGFR mutation carriers was provided to 85% of all eligible. After a median follow up period of 15.9 months for EGFR mutated cases the hazard ratio for overall survival of EGFR-mutated NSCLC treated with TKIs was 0.55(0.49-0.63, p<0.0001) when compared with EGFR wild-type(WT) tumors under usual care. After adjusting for age, sex, ethnicity, smoking history and tumor histology, all of which had an independently significant effect on survival, the HR for TKI-treated, EGFR-mutated tumors, was 0.63 (0.55-0.71, p<0.0001). Treating EGFR-WT cases with TKIs yielded a high HR=1.32 (1.19-1.48).
Conclusions:
TKIs given to EGFR mutated advanced NSCLC demonstrated a substantial survival benefit for at least five years. Squamous histology, smoking, male sex and Arab ethnicity were associated with higher NSCLC mortality hazard. Treating non-EGFR-mutated NSCLC with TKIs seems detrimental. Statement of Significance: • TKIs given to EGFR mutated advanced NSCLC demonstrated a substantial survival benefit for at least five years but not much longer. • Treating non-EGFR-mutated NSCLC with TKIs seems detrimental and should probably be avoided. • Squamous histology of non-small cell lung cancer, smoking history, male sex and Arab ethnicity were associated with altogether higher NSCLC mortality hazard.
Insights
Tyrosine kinase inhibitors (TKIs) significantly improve survival in patients with EGFR-mutated non-small cell lung cancer (NSCLC). However, TKIs appear detrimental for EGFR wild-type NSCLC, highlighting the importance of targeted therapy selection.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- A significant proportion of non-small cell lung cancer (NSCLC) cases harbor EGFR mutations, making them candidates for targeted tyrosine kinase inhibitor (TKI) therapy.
- Understanding the long-term survival impact of TKIs in EGFR-mutated NSCLC is crucial for optimizing treatment strategies.
Purpose of the Study:
- To evaluate the long-term survival outcomes of patients with advanced NSCLC and EGFR mutations treated with TKIs.
- To assess the efficacy and potential harm of TKIs in both EGFR-mutated and EGFR wild-type (WT) NSCLC.
Main Methods:
- A cohort of 3,062 advanced NSCLC patients underwent free tumor EGFR mutation testing.
- EGFR mutations were identified using RT-PCR and fragment analysis.
- Comprehensive electronic medical records (EMRs) were utilized to gather treatment and clinical status data.
Main Results:
- Of 3,062 cases, 481 (15.7%) had somatic EGFR mutations. 85% of eligible EGFR mutation carriers received TKI treatment.
- TKI treatment in EGFR-mutated NSCLC was associated with a significant reduction in overall survival hazard ratio (HR=0.55, p<0.0001) compared to EGFR WT tumors.
- Adjusting for clinical factors, TKI-treated EGFR-mutated NSCLC showed a sustained survival benefit (HR=0.63, p<0.0001), while TKIs in EGFR-WT NSCLC increased mortality risk (HR=1.32).
Conclusions:
- TKIs provide a substantial and sustained survival benefit for patients with EGFR-mutated advanced NSCLC.
- Treatment with TKIs for non-EGFR-mutated NSCLC appears to be detrimental and should be avoided.
- Factors such as squamous histology, smoking, male sex, and Arab ethnicity are associated with increased NSCLC mortality risk.
