Emulated target trial of osimertinib versus second-gnerations EGFR-TKIs in metastatic EGFR-mutant non-small cell lung cancer

Direct real-world comparisons between osimertinib and second-generation EGFR-TKIs are lacking. An emulated target trial using the TriNetX database compared osimertinib versus second-generation EGFR-TKIs for newly diagnosed metastatic EGFR-mutant non-small cell lung cancer (NSCLC). After 1:1 propensity score matching, 777 patients in the first-line osimertinib arm were compared with 777 patients in the second-generation TKI arm. The primary outcome was overall survival (OS). First-line osimertinib demonstrated significantly longer median OS compared with second-generation TKIs (53.4 versus 33.2 months; HR 0.618). Sequential therapy with second-generation TKI followed by osimertinib achieved similar OS but was associated with higher toxicity. Patients with brain metastases derived greater benefit from osimertinib (HR 0.563). Osimertinib also significantly reduced rates of hospitalization, intensive care unit admissiong, and severe infections, generating substantial health care savings despite higher drug costs. The authors conclude that first-line osimertinib provides prolonged OS and economic benefit over second-generation TKIs.