The Progression Patterns and Subsequent Treatments of First‐Line Immunotherapy in Advanced Non‐Small Cell Lung Cancer: A Retrospective Cohort Study

ABSTRACT Background In metastatic non‐small cell lung cancer (NSCLC) patients receiving first‐line immune checkpoint inhibitors (ICIs), the real‐world progression patterns and subsequent treatment outcomes remain controversial. Methods We retrospectively analyzed patients with stage IV NSCLCs treated with first‐line immunotherapy between January 2017 and June 2023. Clinico‐demographic and treatment data were obtained from an electronic medical record system. Progression patterns were categorized by: (1) Progression in different organs; (2) Progression in existing or new lesions; and (3) Oligoprogression versus systemic progression. Survival was assessed using the Kaplan–Meier method and Cox proportional hazards models. Results Among 157 patients, 67.5% experienced systemic progression, and 49.0% had progression in existing lesions. The most common organs with progression were the lung (81.5%), lymph nodes (35.0%), and pleural effusion (24.2%). Median post‐progression survival (PPS) was superior in oligoprogression versus systemic progression (22.4 vs. 10.9 months, p = 0.012). Patients with extrapulmonary progression (8.2 vs. 22.9 months, p < 0.001) or progression in new lesions (9.6 vs. 25.3 months, p = 0.029) showed decreased PPS. In multivariate Cox regression, ECOG PS of 2–4 (HR: 2.26, p = 0.003), tumor stage of IVB (HR: 1.74, p = 0.013), and extrapulmonary progression (HR: 2.05, p = 0.002) were associated with decreased PPS. Subsequent treatments containing ICIs improved survival compared to regimens without ICIs (29.0 vs. 11.3 months, p = 0.004), particularly in patients with systemic progression (19.3 vs. 9.2 months, p = 0.013). Conclusion Most metastatic NSCLCs on first‐line immunotherapy experienced systemic progression. Oligoprogression and progression only in existing lesions showed better prognoses, whereas extrapulmonary progression indicated worse survival. Subsequent ICI‐containing treatments had improved survival.