Epidermal growth factor receptor (EGFR) mutated lung cancer refers to non-small cell lung cancer (NSCLC) that harbors specific activating mutations in the EGFR gene, most commonly exon 19 deletions and exon 21 L858R point mutations.
These mutations drive tumor growth and predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs), which are targeted therapies.
A tyrosine kinase receptor.
EGFR-positive lung cancer represents about 10-15% of lung cancers in the United States and most often appears in the adenocarcinoma subtype of non-small cell lung cancer .
However, in Asian populations, the incidence of EGFR mutations is substantially higher .
Two common EGFR mutations are EGFR exon 19 deletions and EGFR L858R point mutations .
These classic mutations respond well to targeted therapies.
Rarer types that are treated differently than the more common EGFR mutations.
The major example is EGFR exon 20 insertions, which don’t respond to the typical treatment for EGFR-positive lung cancer called tyrosine kinase inhibitors (TKIs) .
Osimertinib, a third-generation EGFR TKI, is the standard therapy for previously untreated EGFR-mutated non-small cell lung cancer patients.
Third generation EGFR tyrosine kinase inhibitors are the standard first line therapy for patients with metastatic disease, however, acquired resistance to EGFR-TKI innevitably develops.
Examples of EGFR-inhibitors include: osimertinib (Tagrisso), afatanib (Gilotrif), erlotinib (Tarceva), and lazertinib (Lazcluze) .
In some instances, doctors may recommend combining an EGFR inhibitor with a different type of therapy as an initial treatment.
Combinations may include osimertinib (Tagrisso) combined with chemotherapy or lazertinib (Lazcluze) combined with amivantamab (Rybrevant) .
Two EGFR inhibitors, amivantamab (Rybrevant) and mobocertinib (Exkivity), received approval to treat locally advanced or metastatic tumors with EGFR exon 20 mutations after progression on chemotherapy .
Amivantamab is a bispecific antibody that works by simultaneously binding and blocking the activity of EGFR and the MET protein .
Resistance inevitably hinders patient prognosis.
When resistance develops, it is recommended that doctors repeat biomarker testing, either through a tissue or liquid biopsy to see if there is a new mutation that will help determine which treatment to suggest.
Patients with lung cancers with EGFR mutations tend to have a minimal to no smoking history , though the mutations can appear in patients with smoking histories as well.
EGFR is a receptor tyrosine kinase involved in cell proliferation and survival.
Mutations in the EGFR gene, especially exon 19 deletions and exon 21 L858R, result in constitutive activation of the receptor’s kinase domain, leading to oncogenic signaling.
These mutations are found in approximately 10–20% of NSCLC cases in White patients and up to 50% in Asian patients, with a higher prevalence in adenocarcinoma histology, never-smokers, and women.
Patients with these EGFR mutations respond well to EGFR TKIs such as osimertinib, erlotinib, gefitinib, afatinib, and dacomitinib, with improved progression-free survival and symptom control compared to chemotherapy.
Less common EGFR mutations (e.g., exon 20 insertions, S768I, L861Q, G719X) have variable sensitivity to TKIs and may require mutation-specific therapy selection.
EGFR mutation testing is recommended for all patients with metastatic NSCLC to guide therapy, regardless of clinical characteristics, as targeted treatment can significantly improve outcomes.
Resistance to EGFR TKIs often develops, most commonly through the T790M mutation, which can be targeted with third-generation TKIs like osimertinib.
In patients with EGFR mutated advanced or metastatic NSCLC that has progressed after previous EGFR-TKI therapy progression free survival and overall survival outcomes are significantly better with sacitizumab than with platinum based chemotherapy.
Among patients with EGFR mutated advanced NSCLC, first line treatment with osimertinib plus platinum-pemetrexed led to significantly longer overall survival than osimertinib monotherapy and was associated with increased risk of reversible adverse events of grade 3 or higher.