The evolving landscape of leptomeningeal metastases from NSCLC: an international, contemporary, multicenter cohort study
Menée à partir de données 2007-2024 portant sur 2 052 patients présentant des métastases leptoméningées ayant pour origine un cancer du poumon non à petites cellules, cette étude de cohorte multicentrique analyse les caractéristiques clinicopathologiques de la maladie, les stratégies thérapeutiques et la survie globale associée
Background: Leptomeningeal metastatic disease (LMD) represents a devastating complication of NSCLC with poor prognosis. Our understanding of LMD is limited in the era of molecular testing and emerging therapeutic options for lung cancer.
Methods: We conducted an international, multicenter retrospective study involving eight institutions across Asia, United States, and Europe. Patients diagnosed with LMD from advanced NSCLC were identified (2007 to 2024). Clinicopathologic characteristics, treatment patterns, and outcomes were analyzed. The primary endpoint was overall survival from the LMD diagnosis (LMOS).
Results: A total of 2,052 patients with NSCLC and LMD were included and analyzed by molecular subtypes: EGFR (n=1,610), ALK (n=141), other actionable genomic alterations (other-AGA; n=137), and non-AGA (n=164). The cumulative prevalence of LMD by molecular subgroups were EGFR, 11.1%; ALK, 11.2%; ROS1, 16%; ERBB2, 12.3%, non-AGA, 3.6%. A higher proportion of LMD was diagnosed greater than 3 years after initial metastatic diagnosis. By EANO ESMO diagnostic criteria, Type I (CSF cytology positive) had significantly shorter LMOS than Type II (MRI and/or symptom positive). Median LMOS was 10.9 months (95%CI 10.0-11.8 months) in all patients. Compared with historical cohorts, patients demonstrated improved LMOS in contemporary cohorts (7.3 vs. 11.5 months, p < 0.0001), across all molecular subtypes. In AGA NSCLC, TKIs were associated with improved LMOS (HR=0.39 95% CI [0.31-0.48)] p < 0.0001). Immune checkpoint inhibitors (ICIs) conferred survival benefit in non-AGA patients (HR=0.45, 95%CI [0.25-0.84], p =0.012). For EGFR-mutated cohort, CNS-penetrant TKIs usage delayed LMD onset (p < 0.0001). Continued CNS-penetrant TKIs after LMD diagnosis was associated with longer LMOS (12.4 vs. 6.0 months, p<0.0001).
Conclusion: The prevalence of LMD is rising, largely due to prolonged survival in advanced NSCLC. Contemporary systemic treatments, including TKIs and ICIs, were the main contributors to delayed LMD onset and improved LMD survival.
Annals of Oncology , résumé, 2025