Aumolertinib Versus Osimertinib as First‐Line Treatment for EGFR ‐Mutant Non‐Small Cell Lung Cancer: A Retrospective Real‐World Multicenter Study

ABSTRACT

While third‐generation EGFR tyrosine kinase inhibitors (TKIs) improve outcomes in EGFR‐mutant NSCLC, optimal selection between these agents remains uncertain. This real‐world study compares the efficacy and safety of aumolertinib with those of osimertinib in the first‐line treatment setting. We retrospectively analyzed 109 EGFR‐mutant (exon 19del/L858R) NSCLC patients treated with first‐line aumolertinib ( n  = 53) or osimertinib ( n  = 56) across four tertiary hospitals (2016–2023). The primary end points included progression‐free survival (PFS) and safety; secondary end points encompassed overall survival (OS), objective response rate (ORR), and predictive biomarker identification through subgroup analyses. Aumolertinib demonstrated superior median PFS compared to osimertinib (34.4 vs. 26.9 months; HR 0.52, 95% CI 0.29–0.92, p  = 0.031), with comparable OS (HR 0.76, 95% CI 0.27–2.15, p  = 0.60). No significant differences emerged in primary lesion ORR (33.96%, 18/53 vs. 42.86%, 24/56) or adverse event (AE) rates (37.7%, 20/53 vs. 39.3%, 22/56). Subgroup analyses confirmed enhanced PFS benefit with aumolertinib in exon 19del‐mutant (HR 0.43, 95% CI 0.21–0.87, p  = 0.02) and co‐mutation‐negative (HR 0.53, 95% CI 0.25–1.14, p  = 0.08) populations. Subgroup analysis identified age < 65 years (HR 0.46, 95% CI 0.22–0.99, p  = 0.046), brain metastases (HR 0.24, 95% CI 0.09–0.66, p  = 0.006), and exon 19del status (HR 0.43, 95% CI 0.2–0.89, p  = 0.023) as independent PFS predictors. Regarding safety, aumolertinib showed a lower overall incidence of liver dysfunction compared to osimertinib (9.43%, 5/53 vs. 14.29%, 8/56), with Grade ≥ 3 events being rare (1.89%, 1/53). Given that liver function is a critical determinant of prognosis, the manageable hepatic safety profile of aumolertinib supports its long‐term clinical utility. Our study demonstrated a clinically meaningful PFS advantage of aumolertinib over osimertinib in treatment‐naïve EGFR‐mutant NSCLC, particularly for exon 19del‐driven and co‐mutation‐negative disease, while maintaining equivalent safety. These findings provide valuable real‐world evidence supporting the use of aumolertinib as a first‐line therapy, contributing to the optimization of treatment selection and AE management. While these subgroup‐specific results offer hypothesis‐generating insights into potential biomarkers for therapeutic individualization, these preliminary findings require further validation in larger, prospective cohorts.