Comprehensive real-world utilization, treatment trajectories, and outcomes of immune checkpoint inhibitors across cancer types: the multicenter FAIR-ICI cohort

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, yet evidence on their utilization, treatment trajectories, and effectiveness in routine clinical practice remains limited. We characterized real-world ICI use and outcomes across cancer types using the multicenter FAIR-ICI cohort and explored differences between real-world and pivotal trial outcomes. Methods: We conducted a retrospective cohort study of adults receiving ICIs across four Belgian hospitals. Structured and unstructured electronic health record data were harmonized using the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) and natural language processing. We evaluated overall survival (OS), time on treatment (ToT), time to next treatment (TTNT), ICI discontinuation (>12-week treatment gap without re-initiation), and post-discontinuation survival. OS was descriptively compared with pivotal trials, and prognostic factors were assessed using multivariable Cox regression. An interactive public dashboard was developed to enable exploration of cohort characteristics, treatment patterns, and outcomes. Results: Among 3,231 ICI-treated patients, 2,514 (77.8%) had metastatic disease. Among metastatic patients, 568 (22.6%) discontinued ICI without subsequent systemic therapy. Median post-discontinuation OS was 21.4 months (95% CI 16.5-37.2), with 49.1% alive at 24 months. ToT and TTNT were generally shorter than OS, particularly in melanoma (median OS 78 months; ToT 7 months; TTNT 26 months). Real-world survival was frequently less favorable than in pivotal trials. ECOG >=2 was associated with poorer OS than ECOG 0-1 (adjusted HR 2.18, 95% CI 1.82-2.60). In NSCLC patients receiving pembrolizumab plus chemotherapy, survival with ECOG 0-1 more closely approximated trial outcomes, whereas survival with ECOG >=2 was substantially poorer. Conclusions: Real-world ICI treatment trajectories extend beyond active treatment, with some patients experiencing prolonged survival after discontinuation. Differences between real-world and trial outcomes highlight the importance of patient characteristics, particularly performance status, when interpreting trial evidence in routine care. FAIR-ICI provides a scalable framework for evaluating real-world immunotherapy effectiveness, treatment trajectories, and future investigations of treatment-related toxicity.