OBJECTIVES: Aumolertinib, an investigational third-generation EGFR inhibitor (EGFRi), has been developed as a first-line treatment for patients with advanced EGFR mutation-positive NSCLC. Aumolertinib and osimertinib, the only approved third-generation EGFRi for this population, have both demonstrated superior safety and efficacy compared to first-generation EGFRis. As no randomized clinical trial (RCT) has directly compared aumolertinib and osimertinib, we conducted an indirect treatment comparison using first-generation EGFRis as the anchor.

METHODS: We used patient-level data from the phase 3 RCT of aumolertinib vs gefitinib (AENEAS) and published data from the phase 3 RCT of osimertinib vs gefitinib or erlotinib (FLAURA) to conduct an anchored simulated treatment comparison (STC). The STC allowed for control of observed potential effect modifiers and prognostic factors that were imbalanced across trials. Outcomes included investigator-assessed progression-free survival (PFS), overall survival (OS), time to treatment discontinuation (TTD), and select adverse event (AE) categories.

RESULTS: For PFS, the primary efficacy endpoint of both RCTs, the hazard ratio (HR) for aumolertinib vs osimertinib was 0.98 (95% CI: 0.68 –1.42), suggesting no difference. For OS, the HR showed a numerical difference favoring aumolertinib (0.73 [95% CI: 0.44 – 1.22]); however, OS data from AENEAS were not mature at the time of analysis. For TTD, the HR was 1.05 (95% CI: 0.74 – 1.49), suggesting no difference between treatments. For AEs leading to dose interruption and to dose reduction, the odds ratios were 0.63 (95% CI: 0.31 – 1.26) and 1.11 (95% CI: 0.26 – 4.69), respectively.

CONCLUSIONS: In the absence of a head-to-head comparison between aumolertinib and osimertinib, this indirect comparison found no statistically meaningful difference in PFS, OS, TTD, and AEs leading to an event between the two treatments.