Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, with most cases diagnosed at advanced stages. Immune checkpoint inhibitors (ICIs), especially PD-1/PD-L1 inhibitors, have transformed treatment paradigms, yet real-world data on their efficacy and post-progression strategies remain limited. This retrospective cohort study analyzed 208 patients with advanced NSCLC, of whom 104 received chemotherapy alone and 104 received chemo-immunotherapy. The primary endpoint was progression-free survival (PFS); overall survival (OS) was secondary. Kaplan–Meier analysis, log-rank tests, and Cox proportional hazards models were employed. Subgroup analyses assessed the impact of metastatic sites, smoking status, and adverse events. Combination therapy significantly improved median PFS (9.7 vs. 3.7 months; P < 0.001) and OS (17.8 vs. 10.3 months; P < 0.001) compared to chemotherapy alone. The 3-year OS rate was notably higher in the combination group (31.7% vs. 12.2%). Poor ECOG status, lymph node metastases, and single-agent chemotherapy were linked to shorter PFS in the chemotherapy group. In the combination group, smoking, liver metastases, and severe adverse events were independent predictors of worse PFS. Among patients receiving second-line treatment, prior PD-1 inhibitor exposure was associated with longer PFS but not OS. In this retrospective real-world cohort of advanced NSCLC, ICIs combined with chemotherapy were associated with longer PFS and OS compared with chemotherapy alone, although residual confounding due to baseline imbalances and the non-randomized design cannot be excluded. These findings support the use of chemo-immunotherapy in appropriate patients and highlight the need for personalized, biomarker-driven strategies to address resistance and improve post-progression management.
Lu et al. (2026) studied this question.