Doublets versus single-agent therapy as first-line therapy for elderly patients with advanced non-small cell lung cancer? A systematic review of randomised controlled trials.

INTRODUCTION Although the standard treatment for advanced non-small cell lung cancer (NSCLC) patients is platinum-based doublet chemotherapy, single-agent therapy is still preferred in elderly patients. Comparison of the efficacy of various combinations of doublets with single-agent chemotherapy is somehow contradictory. This study conducted a systematic review to evaluate the efficacy and tolerability of the third-generation agent-based doublets vs. single-agent chemotherapy in elderly NSCLC patients. METHODS Electronic (PubMed, EMBASE and Cochrane Library database) and manual searches were conducted to collect data from published, randomised, phase 2 and 3 trials which compared doublets with a third-generation single-agent chemotherapy in elderly patients. Pooled relative risks (RRs) were calculated for the incidences of overall response rate (ORR), 1-year survival rate (1-y SR), and grade 3/4 toxicities. RESULTS Seven eligible trials (2219 patients) were selected from 1170 studies that were initially identified. A significant difference in ORR favouring doublets over single agents was observed [RR, 1.59; 95% confidence interval (95% CI), 1.36-1.86; p < 0.0001] with a slightly, but not significantly improved 1-y SR (RR, 1.19; 95% CI, 0.98-1.45, p = 0.007). Subgroup analysis suggested that platinum (RR, 1.94; 95% CI, 1.47-2.55, p < 0.0001) or non-platinum- (RR, 1.45; 95% CI, 1.20-1.75, p < 0.0001) based doublets could improve ORR, and the grade 3/4 thrombocytopaenia (RR, 6.64; 95% CI, 1.78-24.86, p = 0.005) and anaemia (RR, 2.86; 95% CI, 1.62-5.05, p < 0.0001) were preferred to occur in platinum-based doublets. CONCLUSIONS Doublets appear to be more effective and tolerable than single-agent therapy for treating elderly advanced NSCLC patients, and therefore could be considered as a treatment option for elderly populations with good physical status.