Improved survival and rising incidence: insights from the largest retrospective study on leptomeningeal metastases in patients with NSCLC
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
Leptomeningeal metastatic disease (LMD) is a relatively rare but devastating manifestation of non-small cell lung cancer (NSCLC), historically associated with poor survival and limited benefit from systemic therapy.1 Data on patients with NSCLC and LMD remain scarce, as these patients are generally excluded from clinical trials.2 Therefore, the work of Zheng et al. represents a significant contribution by providing the largest and most comprehensive retrospective analysis of LMD in NSCLC to date. By including 2,052 patients (21.3% synchronous LMD) across multiple continents between 2007 and 2024, they provide valuable insights into the evolving epidemiology of LMD and outcomes on newer systemic treatments such as tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI).3
The study demonstrates a meaningful improvement in median overall survival (OS) after LMD diagnosis in the contemporary (2014-2024) versus historical cohort (2007-2013): 7.3 (95% CI 5.1–9.5) versus 11.5 months (95% CI 10.4-12.4). This benefit occurred across molecular subgroups, including EGFR-mutated (n=1610), ALK-rearranged (n=141), other actionable genomic alterations (other-AGA, n=164), and those without AGA (n=164). The best OS was seen for the first two subgroups, probably due to newer-generation, central nervous system (CNS) penetrating TKI.
Importantly, the study suggests a rising cumulative prevalence of LMD, with updated rates of 11.1% in EGFR-mutated and 3.6% in non-AGA NSCLC, compared to previously reported rates of 9% and 2%, respectively.3,4 Additionally, prevalence rates were provided for ALK (11.2%), ROS1 (15.7%), ERBB2 (12.3%), and RET (4.6%). These percentages likely reflect improved diagnostics and prolonged survival, allowing more time for LMD to develop.
Annals of Oncology , éditorial, 2025