Non-platinum doublets were as effective as platinum-based doublets for chemotherapy-na⟨ve advanced non-small-cell lung cancer in the era of third-generation agents

The aim was to compare the efficacy between doublets of third-generation agents (non-platinum) and doublets of platinum plus a third-generation agent (platinum-based) for chemotherapy-na < ve advanced non-small-cell lung cancer (NSCLC). We conducted a literature-based meta-analysis to compare the efficacy between doublets of third-generation agents and doublets of platinum plus a third-generation agent for chemotherapy-na < ve advanced NSCLC. The primary end point was overall survival, and the secondary end points were progression-free survival (PFS) and response rate. Subgroup analyses were also conducted by different non-platinum doublet regimens or different platinum-based doublets. A descriptive review for toxicity was performed. Sixteen randomized controlled trials were identified ultimately. Results demonstrated that the efficacy of non-platinum doublets was comparable with platinum-based doublets according to the overall survival (HR = 1.03, 95 % CI = 0.98-1.08, p = 0.29). Subgroup analyses by different non-platinum doublets also showed the efficacy of all the third-generation doublets, such as vinorelbine plus gemcitabine, vinorelbine plus paclitaxel, gemcitabine plus paclitaxel, and gemcitabine plus docetaxel, was comparable with platinum-based doublets (HR = 1.00, 95 % CI = 0.78-1.27, p = 0.98; HR = 0.97, 95 % CI = 0.80-1.18, p = 0.79; HR = 1.05, 95 % CI = 0.99-1.12, p = 0.11; HR = 1.01, 95 % CI = 0.92-1.10, p = 0.87; respectively). Subgroup analyses by different platinum-based doublets indicated that the efficacy of the third-generation doublets were equal to both cisplatin-based doublets and carboplatin-based doublets (HR = 1.08, 95 % CI = 1.00-1.17, p = 0.05; HR = 1.00, 95 % CI = 0.94-1.05, p = 0.94; respectively). The secondary end points indicated that platinum-based doublets might have an advantage in PFS but not in response rate (HR = 1.06, 95 % CI = 1.01-1.12, p = 0.03; RR = 0.99, 95 % CI = 0.90-1.08, p = 0.81; respectively). Non-platinum doublets were as effective as platinum-based doublets with different toxicity profile for chemotherapy-na < ve advanced NSCLC in the era of third-generation agents.