Real-World Evidence of First- or Second-Line Immune Checkpoint Inhibitors Versus Chemotherapy in Advanced NSCLC: A Prospective Pragmatic Multicenter Korean Study

초록

Introduction Immune checkpoint inhibitors (ICIs) have become the standard first-line treatment for advanced NSCLC. However, prospective real-world evidence comparing ICI-based therapy with chemotherapy remains limited. We evaluated the effectiveness and safety of ICI-based regimens versus chemotherapy in patients with advanced NSCLC. Methods In this nationwide prospective pragmatic study, patients with advanced or metastatic NSCLC who received first- or second-line ICIs with or without chemotherapy (ICI ± C) or chemotherapy alone were included. The ICI ± C cohort was prospectively enrolled, whereas the chemotherapy cohort was retrospectively assembled as a historical control. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included the objective response rate, safety, and subgroup analyses. Results Among 1520 patients, 1234 received first-line therapy (ICI ± C, N = 525; chemotherapy, n = 709) and 286 received second-line therapy (ICI, n = 262; chemotherapy, n = 24). In the first-line setting, ICI ± C significantly improved survival compared with chemotherapy, with a median PFS of 8.1 versus 5.1 months (hazard ratio [HR] = 0.59, 95% CI: 0.52–0.67) and a median OS of 20.1 versus 9.0 months (HR = 0.47, 95% CI: 0.40–0.54). The objective response rate was 41.0% with ICI ± C and 11.4% with chemotherapy. In the second-line setting, PFS was similar (2.1 versus 3.6 mo; HR = 1.05), whereas OS was longer with ICIs (10.9 versus 6.0 mo; HR = 0.60). Multivariable Cox analyses confirmed that ICI ± C remained independently associated with improved survival (adjusted HR = 0.44 for OS and 0.58 for PFS). Treatment-related adverse events were more frequent with ICI ± C but were generally manageable. Conclusion In this large prospective real-world cohort, ICI-based therapy significantly improved survival outcomes compared with chemotherapy in advanced NSCLC, particularly in the first-line setting, supporting the effectiveness of immunotherapy-based strategies in routine clinical practice. © 2026 The Authors.

키워드