Maintenance Treatment With Different Strategies in Advanced Non–Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Abstract

A meta-analysis of all relevant randomized controlled trials (RCTs) was performed to assess the role of maintenance therapy with either a continuation or a switch strategy in the treatment of non–small-cell lung cancer and to investigate improvement in overall survival (OS) and progression-free survival (PFS). Depending on the tumor histologic type (squamous or nonsquamous), OS and PFS were also investigated. We used electronic databases to search for publications reporting RCTs comparing maintenance therapy and placebo or observation from January 1990 to March 2012. The primary endpoint of OS and the secondary endpoint of PFS were analyzed. Hazard ratios (HRs) with their 95% confidence intervals (CIs) were derived. Eleven trials of 4790 patients were eligible for this analysis. A trend of improved OS was found in continuation maintenance therapy, despite a lack of statistical significance (HR 0.82; 95% CI, 0.66-1.01; P = .06). Improved OS with statistical significance was seen in switch maintenance therapy (HR, 0.80; 95% CI, 0.72-0.90; P = .0002). PFS benefit was found with both continuation (HR, 0.54; 95% CI, 0.46-0.63; P < .00001) and switch maintenance therapy (HR, 0.64; 95% CI, 0.59-0.70; P < .00001). The squamous subgroup analysis demonstrated no statistically significant differences in either OS (HR, 0.91; 95% CI, 0.63-1.30; P = .60) or PFS (HR, 0.80; 95% CI, 0.58-1.10; P = .17), whereas the nonsquamous subgroup analysis revealed an improvement in both OS (HR, 0.78; 95% CI, 0.64-0.94; P = .009) and PFS (HR, 0.56; 95% CI, 0.50-0.63; P < .00001). Maintenance therapy was associated with higher drug-related grade 3 or greater toxic effects but without harming the patients' quality of life. Maintenance therapy with either a continuation or a switch strategy significantly increased PFS but OS was significantly improved only with the switch strategy. Patients with a nonsquamous histologic subgroup seemed to be more suitable for maintenance therapy.