Efficacy and safety of combination therapy versus monotherapy in advanced non-small cell lung cancer: A meta-analysis of overall survival and progression-free survival.

Abstract

e20612 Background: Combination therapies, such as immune checkpoint inhibitors (ICIs) with chemotherapy or EGFR-TKI-based combinations, improve outcomes for advanced non-small cell lung cancer (NSCLC). This meta-analysis evaluates the efficacy of combination therapy versus monotherapy in improving overall survival (OS) and progression-free survival (PFS), with an analysis of safety outcomes. Methods: A systematic review identified three studies reporting OS, PFS, and safety outcomes for patients treated with combination therapy versus monotherapy in advanced NSCLC. Fixed-effect meta-analyses calculated pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Statistical significance was assessed using Z-scores, and heterogeneity was evaluated with I² statistics. Median survival improvements were derived from reported data. Results: For OS, combination therapy significantly reduced mortality risk, with a pooled HR of 0.63 (95% CI: 0.50–0.79). Median OS increased by an average of 3.8 months with combination therapy compared to monotherapy (e.g., 25.8 vs. 19.8 months in Yan et al. (2019) and 18.6 vs. 8.47 months in Chen et al. (2021)). For PFS, combination therapy significantly delayed progression, with a pooled HR of 0.61 (95% CI: 0.49–0.75). Median PFS increased by an average of 1.9 months, with improvements like 7.9 vs. 5.9 months in Yan et al. (2019), 6.77 vs. 3.47 months in Tsai et al. (2022), and 6.37 vs. 3.47 months in Chen et al. (2021). Heterogeneity was low for OS (I² = 15%) and PFS (I² = 18%). Grade 3–4 adverse effects occurred in 48% of combination therapy patients compared to 27% with monotherapy, with common toxicities including fatigue, neutropenia, and rash. Conclusions: Combination therapy significantly improves OS and PFS compared to monotherapy in advanced NSCLC, with average survival gains of3.8 months for OS and 1.9 months for PFS. These benefits are offset by higher rates of grade 3–4 adverse effects, underscoring the need for strategies to balance efficacy and safety. Summary of individual and pooled meta-analysis results for (OS) and (PFS) in advanced non-small cell lung cancer (NSCLC) comparing combination therapy to monotherapy. Study Outcome HR (95% CI) Median Survival (Combination Therapy) Median Survival (Monotherapy) Median Survival Improvement Pooled HR (95% CI) Yan et al. (2019) OS 0.77 (0.6-0.99) 25.8 months 19.8 months 6.0 months Yan et al. (2019) PFS 0.75 (0.58-0.96) 7.9 months 5.9 months 2.0 months Tsai et al. (2022) OS 0.66 (0.45-0.97) 6.77 months 3.47 months 3.3 months Chen et al. (2021) OS 0.46 (0.32-0.65) 18.7 months 8.47 months 10.1 months Chen et al. (2021) PFS 0.51 (0.37-0.7) 6.37 months 3.47 months 2.9 months Pooled Meta-Analysis OS 22.2 months 18.4 months 3.8 months 0.63 (95% CI: 0.50–0.79) Pooled Meta-Analysis PFS 7.0 months 5.1 months 1.9 months 0.61 (95% CI: 0.49–0.75)