Safety and Efficacy of Aumolertinib as First-Line Treatment in EGFR-Mutant Lung Adenosquamous Carcinoma: A Multicenter, Single-Arm, Prospective Phase II Study (ARISE Study).

Lung adenosquamous carcinoma (ASC) is a rare histological subtype of non-small cell lung cancer (NSCLC), and prospective data regarding the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in this patient population remain scarce. This prospective, multicenter, single-arm phase II trial (NCT04354961) evaluated the safety and efficacy of aumolertinib as first-line treatment for treatment-naïve patients with stage IV EGFR-mutant ASC. Eligible patients received aumolertinib 110 mg orally once daily, with progression-free survival (PFS) as the primary endpoint and objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety as secondary endpoints. The study was terminated early due to slow accrual, with 12 patients enrolled (median age: 66 years; 58.3% male; 58.3% with EGFR exon 19 deletion). After a median follow-up of 29.0 months, the median PFS and OS were 11.1 months (95% CI, 4.27-NA) and 16.7 months (95% CI, 11.3-NA), respectively. Confirmed ORR and DCR were 58.3% and 83.3%. Treatment-related adverse events (TRAEs) occurred in 75% of patients, with 33.3% experiencing grade 3-4 TRAEs; no treatment-related deaths were observed. Aumolertinib exhibits clinical activity with a manageable safety profile in EGFR-mutant ASC patients. However, its reduced efficacy compared with EGFR-mutant adenocarcinoma highlights the need for histology-specific therapeutic strategies. Trial Registration: NCT04354961.