EGFR

Also known as epidermal growth factor receptor, ERBB1, HER1

Tumour types

non-small cell lung cancer

EGFR encodes the epidermal growth factor receptor; activating mutations occur in a subset of non-small cell lung cancer (NSCLC), predominantly adenocarcinoma.

Common activating alterations are exon 19 deletions and the exon 21 L858R substitution; exon 20 insertions confer reduced or no sensitivity to most first- and second-generation EGFR tyrosine kinase inhibitors.

Clinical significance

Tumors carrying an EGFR exon 19 deletion or L858R substitution are eligible for first-line EGFR tyrosine kinase inhibitor therapy.
fda — FDA-approved product labeling for EGFR TKIs
T790M is a recognized mechanism of acquired resistance to first- and second-generation EGFR TKIs and informs selection of later-generation agents.
pmc — PMC Open Access Subset, oncology literature

FDA-approved treatments

Gilotrif (afatinib) — Metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations [fda]
Rybrevant (amivantamab-vmjw) — Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations [fda]
Tarceva (erlotinib) — Metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations [fda]
Tagrisso (osimertinib) — Metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations (first-line), and EGFR T790M-mutated NSCLC [fda]

Prevalence

Activating EGFR mutations occur in approximately 10%-15% of NSCLC in Western populations and approximately 30%-40% in Asian and never-smoker populations. [fda]

Tests / detection method

NGS, PCR-based mutation panels

Therapeutic pipeline

EGFR-MET bispecific antibodies [fda]
Fourth-generation EGFR tyrosine kinase inhibitors targeting C797S resistance (EGFR C797S) [fda]

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