The optimal therapy strategy for epidermal growth factor receptor‐mutated non‐small cell lung cancer patients with brain metastasis: A real‐world study from Taiwan

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Abstract
Background: The treatment options for epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC) with brain metastases (BMs) include EGFR‐tyrosine kinase inhibitors (TKIs), stereotactic radiosurgery (SRS), whole‐brain radiotherapy, brain surgery, and antiangiogenesis therapy. As treatment options evolve, redefining optimal treatment strategies to improve survival are crucial.Methods: A total of 150 EGFR‐mutant NSCLC patients with BMs who received first‐ or second‐generation EGFR‐TKIs as first‐line treatment between January 2012 and October 2019 were included in this analysis.Results: After multivariate analysis, patients with the graded prognostic assessment for lung cancer using molecular markers (Lung‐mol GPA) ≥3 (hazard ratio [HR]: 0.538, 95% confidence interval [CI]: 0.35–0.83), who received afatinib or erlotinib as first‐line treatment (HR: 0.521, 95% CI: 0.33–0.82), underwent SRS therapy (HR: 0.531, 95% CI: 0.32–0.87), or were sequentially treated with osimertinib (HR: 0.400, 95% CI: 0.23–0.71) were associated with improved overall survival (OS). Furthermore, SRS plus EGFR‐TKI provided more OS benefits in patients with Lung‐mol GPA ≥3 compared with EGFR‐TKI alone in our patient cohort (44.9 vs. 26.7 months, p = 0.005). The OS in patients who received sequential osimertinib therapy was significantly longer than those without osimertinib treatment (43.5 vs. 24.3 months, p < 0.001), regardless of T790 mutation status (positive vs. negative vs. unknown: 40.4 vs. 54.6 vs.43.4 months, p = 0.227).Conclusions: The study demonstrated that EGFR‐mutant NSCLC patients with BMs could be precisely treated with SRS according to Lung‐mol GPA ≥3. Sequential osimertinib was associated with prolonged survival, regardless of T790M status.

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