MMDA-25 INTRACRANIAL EFFICACY OF OSIMERTINIB IN EGFR-MUTATED NON–SMALL CELL LUNG CANCER WITH BRAIN METASTASES: A META-ANALYSIS
Khalid Ahmad Qidwai, Zouina Sarfraz, Namita Ruhela, Ruchit Jain, Fatma Nihan Akkoc Mustafayev, Manmeet S AhluwaliaAbstract
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 estimates of intracranial efficacy remain heterogeneous, particularly across treatment lines.
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 ranged from 23.7-35.2 months in first-line cohorts and 5.9–16.2 months in later-line cohorts. In studies (N = 3) evaluating Osimertinib plus chemotherapy, the sample-size-weighted intracranial median PFS was approximately 23.2 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%).
Conclusions
Osimertinib provides durable intracranial disease control in EGFR-mutated NSCLC with brain metastases, with higher efficacy noted 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.