Checkpoint inhibitors plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

Background: We conducted a meta-analysis to evaluate the efficacy and safety of upfront add-on immunotherapy for advanced non-small cell lung cancers (NSCLC). Methods: We performed a literature search on first-line chemotherapy +/- immunotherapy in NSCLC. We utilized Revman version 5.3 to calculate the estimated pooled hazard ratio for overall survival (OS) and progression-free survival (PFS) and pooled risk ratio for objective response rate (ORR), all-grade and high-grade adverse events with 95% CI. Results: We analyzed 4322 patients. The pooled hazard ratios for OS, PFS and ORR were 0.74 (95% CI: 0.62-0.88; p = 0.0007), 0.62 (95% CI: 0.57-0.68; p = 0.00001) and 1.51 (95% CI: 1.3-1.74; p = 0.00001), respectively. The pooled risk ratios for all-grade and high-grade adverse events were 1.01 (95% CI: 0.99-1.03; p = 0.27) and 1.17 (95% CI: 1.07-1.28; p = 0.0006), respectively. Conclusion: Add-on immunotherapy significantly improves PFS, OS and ORR for the first-line treatment of advanced NSCLC with a reasonable safety profile. Lay abstract: Lung cancer is the most frequent cancer and is the leading cause of cancer mortality worldwide - more than half of the patients presented at late-stage disease, which is associated with limited survival. To treat cancers, we use immune checkpoint inhibitors that release the brakes on the immune system; thus, the immune cells can kill cancer cells better. Multiple clinical trials have tested the role of immune checkpoint inhibitors combined with chemotherapy for lung cancer treatment. Based on these clinical trials, we conducted a systematic review that showed improvement in outcomes with combined chemotherapy and immunotherapy with acceptable adverse events.