Current paradigm of EGFR^ins20 in non-small cell lung cancer: A long way forward

EGFR^ins20 alterations are detected in 5% to 12% of the EGFR mutated subgroup in advanced non-small cell lung cancer. Historically, these alterations have been correlated with worse prognosis among the common EGFR mutation subtypes, which largely respond only to chemotherapy. The availability of new targeted therapies with EGFR^ins20 activity has transformed the precision medicine landscape for patients, with improved outcomes and survival. Previous clinical trials evaluating EGFR holistic targeted therapies, such as erlotinib, gefitinib, and osimertinib, in EGFR^ins20 patients have all failed, requiring a realignment of EGFR^ins20 therapeutic drug development. New clinical trial data on EGFR^ins20-specific targeted therapies have led to US Food and Drug Administration (FDA) approval of amivantamab-vmjw and accelerated FDA approval of sunvozertinib, with more clinical trial drugs currently under investigation. Next-generation sequencing (NGS) testing, including liquid biopsy, should be prioritized to differentiate patients with this subtype and consider the individual EGFR^ins20 variants that may respond differently to available therapeutics.