Abstract 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.
Yu et al. (Fri,) studied this question.