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Updated: Mar 24, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Comprehensive Genomic Profiling Identifies Frequent Drug-Sensitive EGFR Exon 19 Deletions in NSCLC not Identified by
Alexa B Schrock1, Garrett M Frampton1, Dana Herndon2
1Foundation Medicine Inc., Cambridge, Massachusetts.
Purpose:
Reliable detection of drug-sensitive activating EGFR mutations is critical in the care of advanced non-small cell lung cancer (NSCLC), but such testing is commonly performed using a wide variety of platforms, many of which lack rigorous analytic validation.
Experimental Design:
A large pool of NSCLC cases was assayed with well-validated, hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions. From these, 400 cases harboring EGFR exon 19 deletions (Δex19) were identified, and available clinical history was reviewed.
Results:
Pathology reports were available for 250 consecutive cases with classical EGFR Δex19 (amino acids 743-754) and were reviewed to assess previous non-hybrid capture-based EGFR testing. Twelve of 71 (17%) cases with EGFR testing results available were negative by previous testing, including 8 of 46 (17%) cases for which the same biopsy was analyzed. Independently, five of six (83%) cases harboring C-helical EGFR Δex19 were previously negative. In a subset of these patients with available clinical outcome information, robust benefit from treatment with EGFR inhibitors was observed.
Conclusions:
CGP identifies drug-sensitive EGFR Δex19 in NSCLC cases that have undergone prior EGFR testing and returned negative results. Given the proven benefit in progression-free survival conferred by EGFR tyrosine kinase inhibitors in patients with these alterations, CGP should be considered in the initial presentation of advanced NSCLC and when previous testing for EGFR mutations or other driver alterations is negative. Clin Cancer Res; 22(13); 3281-5. ©2016 AACR.
Insights
Comprehensive genomic profiling (CGP) detects EGFR mutations missed by other tests in non-small cell lung cancer (NSCLC). This is crucial for guiding targeted therapy decisions in advanced NSCLC patients.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Accurate detection of EGFR mutations is vital for treating advanced non-small cell lung cancer (NSCLC).
- Current EGFR mutation testing methods vary widely and often lack thorough validation.
- This can lead to missed diagnoses and suboptimal treatment strategies.
Purpose of the Study:
- To evaluate the effectiveness of comprehensive genomic profiling (CGP) in identifying EGFR mutations in NSCLC cases previously tested with other methods.
- To assess the clinical utility of CGP in patients with advanced NSCLC, particularly when initial testing is negative.
Main Methods:
- A large cohort of NSCLC cases underwent CGP for clinical decision-making.
- 400 cases with EGFR exon 19 deletions (Δex19) were identified for further review.
- Pathology reports were analyzed for 250 cases to compare CGP results with previous non-hybrid capture-based EGFR testing.
Main Results:
- CGP identified EGFR Δex19 in 17% of cases that previously tested negative.
- This included 17% of cases where the same biopsy was re-analyzed.
- 83% of cases with C-helical EGFR Δex19 were previously negative, highlighting CGP's sensitivity.
Conclusions:
- CGP effectively detects drug-sensitive EGFR Δex19 mutations missed by prior testing in NSCLC.
- Considering CGP for initial NSCLC workup or when previous tests are negative is recommended.
- EGFR tyrosine kinase inhibitors offer significant benefits to patients identified with these mutations via CGP.
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