Single agent maintenance therapy for advanced stage non-small cell lung cancer: A meta-analysis

Background: Maintenance therapy is a new treatment paradigm for advanced non-small cell lung cancer (NSCLC). We conducted a meta-analysis of randomized studies with single agent maintenance therapy. Methods: An electronic literature search of public databases (MEDLINE, EMBASE, Cochrane library) and manual search of relevant conference proceedings was performed. A formal meta-analysis was conducted using Comprehensive Meta Analysis software (Version 2.0). Outcome data were pooled and reported as hazard ratio (HR). The primary outcome of interest was overall survival (OS) and secondary outcome was progression free survival (PFS). Results: Twelve studies were included (5 meeting abstracts, 7 full manuscripts) with a total of 4286 patients (maintenance arm/control arm - 2449/1837, median age 61. years, males - 69%). The OS (HR 0.86, 95% confidence intervals [CI] 0.80-0.92; P= 0.0003) and PFS (HR 0.80, 95% CI 0.77-0.84; P<0.0001) were superior with maintenance therapy. 'Switch' maintenance was associated with significant OS and PFS improvement (OS HR 0.84, 95% CI 0.77-0.91; P= 0.00026; PFS HR 0.62, 95% CI 0.57-0.67; P<0.0001). Despite a modest improvement in PFS (HR 0.90, 95%CI 0.85-0.95; P= 0.007), "continuation" maintenance was not associated with survival benefit (HR 0.927, 95%CI 0.78-1.09; P= 0.33). Improvements in OS and PFS were observed with both EGFR-targeted agents (HR 0.83, 95% CI 0.74-0.92; P= 0.004; HR 0.64, 95% CI 0.58-0.71 P<0.0001) and cytotoxic agents (HR 0.89, 95% CI 0.80-0.98; P= 0.018; HR 0.85, 95% CI 0.80-0.89; P<0.0001). Conclusions: Single agent maintenance therapy improves overall survival, though statistical significance was only noted with 'switch' maintenance.