Third-generation EGFR-TKI plus pemetrexed-platinum chemotherapy versus TKI monotherapy as first-line treatment for EGFR-mutant lung adenocarcinoma with brain parenchymal metastases

Objective To evaluate the efficacy and safety of first-line third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) combined with pemetrexed-platinum chemotherapy in patients with EGFR-mutant advanced lung adenocarcinoma and brain parenchymal metastases. Methods A bicenter retrospective cohort study was conducted. A total of 150 eligible patients were enrolled and balanced by 1:1 propensity score matching. Tumor response, survival outcomes, and treatment-related adverse events were compared between groups. Results After matching, 60 patients were assigned to each group. The intracranial objective response rate was 78.3% in the combination group versus 61.7% in the monotherapy group (P = 0.046). The median intracranial progression-free survival was 28.3 months in the combination group (hazard ratio = 0.536, 95% confidence interval: 0.350–0.820, P = 0.002). Systemic progression-free survival and overall survival were also significantly prolonged in the combination arm. Adverse events were predominantly chemotherapy-related toxicities and were generally manageable. Conclusion First-line third-generation EGFR-TKI plus pemetrexed-platinum chemotherapy is associated with superior intracranial and systemic survival benefits in EGFR-mutant lung adenocarcinoma patients with brain parenchymal metastases, with a favorable safety profile. This study provides real-world evidence to support clinical treatment decision-making.