Duration of systemic therapy in patients with metastatic EGFR-mutated non-small cell lung cancer and brain metastases

Background — Osimertinib, a third-generation epidermal growth factor receptor (EGFR) inhibitor, has demonstrated strong central nervous system (CNS) activity in EGFR-mutated metastatic non-small cell lung cancer (mNSCLC). We hypothesized that osimertinib would be associated with longer first-line treatment duration than the first-generation EGFR inhibitor gefitinib among patients with brain metastases.

Methods — We performed an observational study using provincial administrative databases. All patients with EGFR-positive mNSCLC treated between 2007 and 2024 who received first-line osimertinib or gefitinib and underwent brain radiotherapy within four weeks of systemic therapy initiation, serving as a surrogate for brain metastasis diagnosis, were included for analysis. The primary outcome was duration of first-line systemic therapy. Secondary outcomes included overall survival (OS) and CNS radiation progression-free survival (CNS-rPFS), estimated using Kaplan-Meier methods. Propensity score matching was used to adjust for baseline differences.

Results — Among 3,541 eligible patients, 481 met inclusion criteria (osimertinib: 222; gefitinib: 259). Median first-line treatment duration was significantly longer with osimertinib than with gefitinib (12.6 vs. 6.4 months; P<0.001). Osimertinib was also associated with longer median CNS-rPFS (21.7 vs. 13.5 months; P<0.001) and OS (24.7 vs. 13.6 months; P<0.001). After propensity score matching (n=412), these differences persisted for treatment duration (12.9 vs. 6.8 months), CNS-rPFS (24.9 vs. 14.5 months), and OS (25.6 vs. 14.6 months), all P<0.001.

Conclusions — In real-world practice, osimertinib is associated with longer first-line treatment duration, improved CNS control, and longer survival compared with gefitinib among EGFR-positive mNSCLC patients with brain metastases.