Efficacy and safety of aumolertinib/icotinib combination therapy for naive EGFR -mutant non–small-cell lung cancer patients with brain metastases: A phase I/II study

BACKGROUND: The benefits of offering first- plus third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for treatment-naive EGFR-mutant non-small cell lung cancer patients (NSCLC) with brain metastases (BMs) are unknown. This trial aims to assess the feasibility, safety, and efficacy of icotinib plus aumolertinib in these patients. METHODS: The phase I/II trial (ChiCTR2100044216) employed a 3 + 3 dose-escalation and dose-expansion design targeting EGFR-mutant NSCLC patients with baseline measurable BMs. Primary endpoints were the recommended phase II dose (RP2D) and feasibility. Major secondary endpoints included median overall survival (OS), systemic and intracranial progression-free survival (PFS and iPFS), objective response rate (ORR and iORR), and safety profile. RESULTS: 24 eligible patients were evaluated with a median follow-up of 41.4 months. The RP2D was 125 mg icotinib three times daily plus 110 mg aumolertinib once daily. Median PFS was 21.1 months (95% CI 14.6-27.6 months) and median OS was 40.8 months (95% CI 29.1-52.5). ORR was 95.8% and the disease control rate (DCR) was 100%. Median iPFS was 22.5 months (95% CI 17.5-27.6 months) with iORR of 91.7% and intracranial DCR of 100%. For safety profile, grade ≥3 treatment-related adverse events (TRAEs) occurred in 37.5% of patients. The most common any-grade TRAEs were increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), and rash. CONCLUSIONS: The combination of aumolertinib and icotinib shows encouraging efficacy and a tolerable safety profile in patients with EGFR-mutant NSCLC and BMs, supporting its potential as a therapeutic option warranting further investigation.