High-dose furmonertinib as first-line treatment for untreated EGFR-mutated advanced NSCLC with central nervous system metastases: A phase 2 trial

Brain metastases in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) frequently contribute to treatment failure. This phase II study aims to evaluate furmonertinib (160 mg daily) in 40 untreated patients with EGFR-mutant NSCLC and central nervous system (CNS) metastases. At a median follow-up of 18.66 months, the blinded independent central-review-assessed median progression-free survival (mPFS) and intracranial PFS are 16.59 months (95% confidence interval [CI]: 12.77-20.41) and 17.83 months (95% CI: 14.16-21.50), respectively. Systemic objective response rate (ORR) is 92.5%, and intracranial ORR is 95.0%, with consistent investigator assessments. Grade ≥3-treatment-related adverse events occur in 15.0% of patients. Exploratory profiling of paired plasma and cerebrospinal fluid reveals significant early molecular response, with high EGFR mutation clearance (85.7% plasma; 66.7% cerebrospinal fluid [CSF]). Furmonertinib shows promising intracranial efficacy with manageable safety as first-line treatment for EGFR-mutated NSCLC with CNS metastases. This study is registered at ClinicalTrials.gov (NCT05379803).