Real-World Evidence of First- or Second-Line Immune Checkpoint Inhibitors Versus Chemotherapy in Advanced NSCLC: A Prospective Pragmatic Multicenter Korean Study
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Institutions: Samsung Medical Center, Sungkyunkwan University, Gyeongsang National University, Gyeongsang National University Hospital, Inje University, Inje University Haeundae Paik Hospital, Inje University Busan Paik Hospital, Seoul National University, Seoul National University Hospital, Kangbuk Samsung Hospital, National Cancer Center, Gachon University, Gachon University Gil Medical Center, Gachon University Medical Center, Ajou University, Konkuk University, Konkuk University Medical Center, Korea University, Korea University Guro Hospital, Keimyung University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,000
Award: G5634365343
OpenAlex ID: W7203893970