e20765 Background: Brain metastases are a major cause of morbidity and mortality in EGFR-mutated non-small cell lung cancer (NSCLC). Osimertinib demonstrates central nervous system (CNS) activity, but intracranial efficacy estimates remain heterogeneous, particularly by treatment line. Methods: Pubmed, Cochrane Library and Scopus were searched for studies reporting intracranial outcomes in adults with EGFR-mutated non-small cell lung cancer and brain metastases treated with Osimertinib. Studies reporting patient-level intracranial objective response rate (ORR) and/or disease control rate (DCR) were included. Pooled intracranial ORR and DCR were estimated using random-effects meta-analyses. Heterogeneity was assessed using the I² statistic. A subgroup analysis was performed for first-line osimertinib. Safety outcomes were pooled when grade ≥3 adverse events were reported. Results: Nine studies with 299 patients were included in the primary analysis. The pooled intracranial ORR across all treatment lines was 62. 1% (95% CI, 45. 2%-76. 5%; I² = 77. 3%), while the pooled intracranial DCR was 92. 5% (95% CI, 86. 8%-95. 8%; I² = 11. 4%). In the subgroup analysis of Osimertinib as first-line, pooled intracranial ORR was 86. 6% (95% CI, 71. 1%-94. 5%; I² = 23. 9%), and pooled intracranial DCR was 97. 5% (95% CI, 76. 5%-99. 8%; I² = 0%). Median overall survival was longer in first-line Osimertinib cohorts (23. 7–35. 2 months) than in later-line cohorts (5. 9–16. 2 months). Across studies reporting safety outcomes (N = 235 patients), the pooled incidence of grade ≥3 adverse events was 11. 0% (95% CI, 5. 0%-22. 5%; I² = 39. 8%). In studies (N = 3) evaluating Osimertinib plus chemotherapy, the sample-size–weighted intracranial median PFS was approximately 23. 2 months. Conclusions: Osimertinib provides durable intracranial disease control in EGFR-mutated NSCLC with brain metastases, with the higher efficacy observed in the first-line setting. These findings support Osimertinib as a CNS-active systemic therapy and underscore the need for CNS-focused endpoints in future trials. Analysis Group Outcome Estimate (95% CI) I² (%) P - Value Overall Intracranial ORR 62. 1% (45. 2–76. 5) 77. 3 <0. 0001 Intracranial DCR 92. 5% (86. 8–95. 8) 11. 4 0. 338 First-line Osimertinib Intracranial ORR 86. 6% (71. 1–94. 5) 23. 9 0. 267 Intracranial DCR 97. 5% (76. 5–99. 8) 0 0. 526 Safety Grade ≥3 adverse events 11. 0% (5. 0–22. 5) 39. 8 0. 156 Osimertinib + Chemotherapy Intracranial Median PFS 23. 2 months (NA) _ _
Ruhela et al. (Thu,) studied this question.