Intracranial efficacy of osimertinib in EGFR -mutated non–small cell lung cancer with brain metastases: A meta-analysis.

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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) _ _

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