First-Line Immune Checkpoint Inhibitors Versus Chemotherapy in Delaying Quality of Life Deterioration in Advanced NSCLC: A Systematic Review and Meta- Analysis

Backgroud: Immune checkpoint inhibitors (ICIs) have transformed first-line treatment for advanced non–small-cell lung cancer (aNSCLC). While overall survival(OS) remains the primary endpoint, health-related quality of life (HRQoL) is a key patient-centered outcome. Time to deterioration (TTD) captures the durability of HRQoL over treatment. This study compared TTD in HRQoL between patients receiving ICI-based therapies and chemotherapy, and conducted exploratory analyses to assess the association between trial-level hazard ratios(HRs) for TTD and OS. Method MEDLINE, CENTRAL, and Scopus were systematically searched from inception to September 2025. Eligible studies included phase II or III randomized clinical trials evaluating first-line ICIs–based therapies(ICI monotherapy, dual ICI combinations, or ICIs combined with chemotherapy) for aNSCLC and reporting TTD in HRQoL.The prespecified primary outcome was hazard ratio (HR) for TTD of global QoL between aNSCLC patients treated with ICI–based therapies and those receiving chemotherapy. Secondary outcomes were HR for TTD of physical and emotional functioning and symptomatology. (PROSPERO registration number: CRD420251266405) Result A total of 6555 aNSCLC patients from 13 randomized trials comparing ICI-based therapies with chemotherapy were included. Compared with chemotherapy, ICIs–based therapies delayed deterioration of global QoL ( HR 0.75, 95% confidence interval [CI] 0.71–0.81; p < 0.0001, I ²=0%). Regimen-specific analyses indicated that Immunochemotherapy delayed TTD in Global QoL over chemotherapy(HR 0.74, 95%CI 0.69–0.80; I ²=0%), whereas no significant benefit in TTD of Global QoL was observed with immunotherapy(HR 0.78, 95%CI 0.58–1.05; I ²=0%), with similar patterns for physical functioning. Across symptom outcomes, ICI based therapies delayed deterioration in several symptoms, including fatigue, pain, cough, dyspnea, and the composite endpoint of cough, chest pain, or dyspnea, while no significant difference was observed for appetite loss. Exploratory analyses further suggested an association between trial-level HRs for TTD of HRQoL and HRs for OS, although these findings should be interpreted cautiously. Conclusion Among patients with aNSCLC, first-line ICI-based therapies significantly delayed deterioration of HRQoL compared with chemotherapy. These findings indicate that ICI-based therapies—particularly immunochemotherapy—are associated with more durable preservation of HRQoL in first-line treatment, complementing their established survival benefits. Exploratory analyses further suggested that trial-level HRs for HRQoL deterioration were positively associated with HR for OS.