EGFRmutated

EGFRmutated describes tumors that harbor activating or clinically relevant mutations in the epidermal growth factor receptor (EGFR) gene. In non-small cell lung cancer (NSCLC), the most common activating mutations are deletions in exon 19 and the L858R substitution in exon 21, which increase signaling through the EGFR pathway and promote tumor growth. These mutations predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Detection relies on molecular testing of tumor tissue or circulating tumor DNA.

EGFR mutations are most extensively studied in NSCLC, particularly adenocarcinoma, and occur more often in never-smokers and individuals of East Asian descent. EGFR alterations also occur in other cancers but are less common; for example, glioblastoma often involves EGFR amplification and the EGFRvIII variant, while in colorectal cancer the role of EGFR mutations is less predictive of TKI response.

In NSCLC with sensitizing EGFR mutations, targeted therapy with EGFR TKIs is standard. First- and second-generation TKIs (gefitinib, erlotinib, afatinib) and the third-generation agent osimertinib are used, with osimertinib increasingly preferred as initial therapy due to superior CNS activity and outcomes. Resistance commonly develops through mechanisms such as the T790M mutation or alternative pathway activation; osimertinib can overcome T790M, but subsequent resistance routes emerge. Upon progression, treatment is guided by rebiopsy or circulating tumor DNA testing and may include chemotherapy or clinical trials. Common side effects include rash, diarrhea, and dry skin.

Overall, EGFRmutated tumors represent a defined molecular subset that benefits from targeted inhibitors, leading to improved progression-free survival in many cases. Ongoing research seeks to overcome resistance and expand testing access.