Screening for brain metastases in patients with advanced non-small cell lung cancer and an actionable genomic alteration: A structured literature review

Background Brain metastases (BM) frequently occur in patients with non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGA). Targeted therapies (TTs) improve outcomes, but differences in BM screening and eligibility criteria across trials make comparisons challenging. While stage IV NSCLC guidelines recommend BM screening, it is not mandatory, and imaging techniques vary. Methods Registrational and phase II/III trials of FDA/EMA-approved TTs for advanced NSCLC with AGA, published since 2012, were included. Main focus of the review was evaluation of baseline brain screening practices across trials. Information on BM follow-up, BM incidence, and BM-related outcomes was retrieved. Results Of 51 trials, 71% mandated baseline BM screening, and 27% mandated follow-up imaging for all patients. MRI was specified for BM assessment in 31% of the trials. BM incidence at baseline was high, up to 40% in the first-line setting. While most trials included patients with BM, eligibility criteria varied, and 43% of trials prespecified BM-related outcomes; 56% of phase III trials used BM as a stratification factor. Conclusion This review highlights the increasing attention to BM screening in NSCLC TT trials. However, substantial heterogeneity remains in BM eligibility, screening, outcomes, and follow-up. Standardizing these aspects in future trials is essential.