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Updated: May 15, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions
Geoffrey R Oxnard1, Peter C Lo, Mizuki Nishino
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02114, USA. Geoffrey_Oxnard@DFCI.harvard.edu
Introduction:
Exon 20 insertions are the third most common family of epidermal growth factor receptor (EGFR) mutations found in non-small-cell lung cancer (NSCLC). Little is known about cancers harboring these mutations aside from their lack of response to EGFR tyrosine kinase inhibitors, impairing the development of effective targeted therapies.
Methods:
NSCLC patients with EGFR genotyping were studied using a mechanism approved by the Institutional Review Board. Cancers with exon 20 insertions were indentified, sequences were characterized, and effectiveness of different treatment regimens was reviewed retrospectively. Clinical characteristics and survival were compared with cancers harboring common EGFR mutations and cancers with wild-type EGFR.
Results:
One thousand eighty-six patients underwent EGFR genotyping from 2004 to 2012. Twenty seven (2.5%) harbored exon 20 insertions, making up 9.2% of all cancers with documented EGFR mutations. Compared with wild-type cancers, those with exon 20 insertions were more commonly found in never-smokers and Asian patients. Insertion sequences were highly variable, with the most common variant (V769_D770insASV) making up only 22% of cases. Median survival of patients with exon 20 insertions was 16 months, similar to the survival of wild-type cancers and shorter than the survival of cancers with common EGFR mutations.
Conclusions:
Patients with EGFR exon 20 insertions have similar clinical characteristics to those with common EGFR mutations but a poorer prognosis. The prevalence of this subset of NSCLC is similar to that of other genotype-defined subsets of lung adenocarcinoma (e.g. those with BRAF mutations, HER2 insertions, ROS1 rearrangements) and is a population of interest for trials of new targeted therapies.
Insights
Epidermal growth factor receptor (EGFR) exon 20 insertions in non-small-cell lung cancer (NSCLC) are common but untreatable with current therapies. These mutations confer a poorer prognosis, highlighting the need for novel targeted treatments.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Exon 20 insertions are a frequent EGFR mutation in non-small-cell lung cancer (NSCLC).
- These mutations are linked to resistance against EGFR tyrosine kinase inhibitors.
- Understanding these mutations is crucial for developing targeted therapies.
Purpose of the Study:
- To identify and characterize EGFR exon 20 insertions in NSCLC patients.
- To evaluate the clinical characteristics and survival outcomes of patients with these mutations.
- To compare outcomes with common EGFR mutations and wild-type EGFR.
Main Methods:
- Retrospective review of NSCLC patients undergoing EGFR genotyping.
- Identification and sequencing of exon 20 insertion mutations.
- Comparison of clinical features and survival data.
Main Results:
- 2.5% of NSCLC patients (27/1086) had EGFR exon 20 insertions.
- These mutations were more prevalent in never-smokers and Asian patients.
- Median survival was 16 months, similar to wild-type but shorter than common EGFR mutations.
Conclusions:
- EGFR exon 20 insertions in NSCLC present similar clinical features but a worse prognosis.
- The prevalence is comparable to other genotype-defined subsets, warranting further investigation.
- This patient group is a key target for novel therapeutic strategies.
