Abstract
Background: Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer and a leading cause of cancer death worldwide. For long, chemotherapy has proved the most appropriate treatment although the advent of immunotherapy, particularly immune checkpoint inhibitors directed against PD-1/PD-L1, marked a turning point in the treatment paradigm for advanced NSCLC. The purpose of this systematic review and meta-analysis is to compare survival outcomes and safety profiles of immunotherapy versus chemotherapy in patients with advanced NSCLC.
Methods: A systematic search was performed in PubMed, Embase, and Cochrane Library databases from 2014-2025 to identify relevant studies. Fifteen studies met predefined inclusion criteria. Hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS), odds ratios (ORs), and adverse event (AE) rates were pooled by random-effects models. We conducted subsequent subgroup analysis of age and PDL1 expression levels. Egger’s test and I² statistic were applied to assess publication bias and study heterogeneity, respectively.
Results: As compared with chemotherapy, immunotherapy was related to significantly better survival. Hazard ratios for OS and PFS favored immunotherapy in all the 15 included studies. Patients >65 years and with PD-L1 expression ≥50% had the greatest survival advantages. The immunotherapy arm also had less grade 3–5 AEs and fewer treatment discontinuations. Moderate studies heterogeneity and minimal publication bias was found. Sensitivity analyses supported the robustness of the findings.
Conclusion: Immunotherapy confers a better clinical benefit compared to chemotherapy for advanced NSCLC, especially in elderly and high-PD-L1 expression patients. These results contribute to the evolving trend of immunotherapy as first-line therapy and underscore the need for biomarker-driven patient selection. More long-term research is needed to confirm these results and to determine the best combination plan