Approved for first line therapy in NSCLC and include erlotinib, afatinib, and gefitinib.
Erlotinib and geftinib are first generation TKIs.
They reversibly bind to the intracellular tyrosine kinase domain, resulting in inhibition of the autophosphorylation of the tyrosine residues.
Afatinib is a second generation TKI that irreversibly targets EGFR (HER!) as well as to HER2 and HER4.
Osimertinib is a third generation TKI.
EGFR TKIs have superior efficacy over platinum doublet chemotherapy in treatment naive patients with NSCLC with EGFR mutations.
Amivantamab is an EGFR-MET, mesenchymal epithelial transition factor bispecific antibody with immune with immune cell directing activity with multiple mechanisms of action, and when added to chemotherapy results and superior efficacy, as compared with chemotherapy alone, first line treatment of patients with advanced NSCLC with EGFR exon 20 insertions.
Lazertinib is a highly selective CNS penetrate third generation EGFR-TKI with efficacy in both activating the EGFR and T790 M mutations.
Amivantamab-lazertinib is superior in efficacy to osertinib as first line treatment in EGFR mutated advanced NSCLC.
Rash is an adverse effect specific to all agents that block the EGFR pathway, including small molecules and monoclonal antibodies.