Doublet vs Single-Agent Maintenance Therapy in the Treatment of Non-Small-Cell Lung Cancer: A Meta-Analysis

BACKGROUND: Several published meta-analyses have confirmed that single-agent maintenance therapy in advanced non-small-cell lung cancer (NSCLC) can prolong time to disease progression and potentially increase overall survival (OS) in comparison to placebo. However, whether doublet maintenance therapy can improve the survival of advanced NSCLC remains undetermined. METHODS: We searched several databases for relevant trials. Prospective randomized controlled trials comparing doublet vs single-agent maintenance therapy in NSCLC patients were included for analysis. Outcomes of interest were OS, progression-free survival (PFS), and incidence of grade 3/4 toxicities. RESULTS: A total of 1,950 advanced-NSCLC patients from six trials were included for analysis. Our results showed that doublet maintenance therapy in NSCLC patients significantly improved PFS (HR 0.74, 95% CI 0.59–0.93; P=0.010), but not for OS (HR 0.95, 95% CI 0.85–1.07; P=0.40) in comparison with single-agent maintenance therapy. Subgroup analysis by maintenance regimen showed that pemetrexed plus bevacizumab maintenance therapy significantly improved PFS, but not OS. In addition, there was no significant risk difference between doublet and single-agent maintenance therapy in terms of grade 3/4 hematologic and nonhematologic toxicities. CONCLUSION: Our study suggests that doublet maintenance therapy in advanced-NSCLC patients demonstrates PFS benefits, but not OS benefits, in comparison with single-agent maintenance therapy. Future trials are suggested to assess the long-term clinical benefit of doublet maintenance treatment in NSCLC patients and its impact on health-related quality of life.