FALCON-Lung: Evolving global real-world treatment choices and outcomes for metastatic NSCLC in different patient populations.

Abstract

1553 Background: Despite rapid global adoption of immune checkpoint inhibitors (ICI) for metastatic non–small cell lung cancer (mNSCLC), real-world treatment access, selection, time on treatment and transitions between regimens remain poorly characterized across health systems and patient populations. Whether observed outcomes are consistent across regions, data sources, and age groups is largely unknown. Addressing these gaps at scale requires a federated analytic approach with standardized analyses across sites, enabling reliable and comparable results while preserving patient privacy. Methods: We launched FALCON (Federated Alliance for Large-scale Cancer Observational Network), the largest federated, most diverse oncology network supporting observational cancer research, and its subnetwork FALCON-Lung. FALCON-Lung includes 23 sites (hospitals, registries, public-private) providing longitudinal cancer data from 2015 onwards standardized to OMOP common data model, from 11 countries in Europe, US and Australia. All sites completed data quality assessments and targeted improvements to improve completeness and overall cancer data quality. Analyses were executed locally using shared analytic code without sharing patient-level data. Results: Among 111,574 NSCLC pts included, 62% developed metastatic disease, of whom 59% initiated antineoplastic drugs within three months; 88% received a guideline-recommended 1 st line regimen. ICI uptake rose sharply between 2017 - 2019; by 2022 59% received ICI (± platinum) in 1 st line. ICI monotherapy showed a tendency toward longer overall survival (OS) compared with platinum (±ICI), although no single regimen demonstrated a consistent advantage across all databases. OS decreased with age across sites. Patients aged ≥81 years were less likely to receive systemic therapy and, when treated, more often received ICI monotherapy. No clear or consistent differences in OS were observed between different treatment regimens in this age group. Conclusions: In this global federated study, ICI uptake showed consistent patterns across sites and regions. OS varied across sites and no consistent survival advantage was observed for ICI regimens, either as monotherapy or in combination, although higher OS with ICI monotherapy was observed in some settings. Older patients (aged ≥81 years) were more frequently treated with ICI monotherapy without a corresponding survival advantage, possibly reflecting real-world treatment selection driven by tolerability rather than biomarkers. Total 18-64y 65-81y ≥81y NSCLC 111,574 36,239 62,328 13,007 Metastatic NSCLC 68,678 24,059 36,397 8,222 1st line systemic therapy 40,619 15,226 21,397 3,980 1st line guideline-approved systemic therapy 35,560 13,458 18,725 3,361 1st line in 2022 (%) ICI monotherapy 17 12 18 32 ICI + platinum doublet 42 43 45 26 Other guideline-approved regimen 41 45 37 43