First-line immune-based combination therapies for advanced non-small cell lung cancer: A Bayesian network meta-analysis

Background: Immune-based combination therapies have revolutionized the first-line treatment for advanced non-small cell lung cancer (NSCLC). However, for the efficacy and safety, the best treatment option is still uncertain.

Methods: We conducted a Bayesian network meta-analysis of randomized controlled trials (RCTs) to evaluate first-line immune-based combination therapies for advanced NSCLC.

Results: Fourteen trials involving 8467 patients were included. For the programmed cell death-ligand 1 (PD-L1) expression non-selective patients, there were no significant differences among all the treatment modes for overall survival (OS), but the ranking profiles indicated that Immunotherapy + Immunotherapy + Chemotherapy (IO + IO + Chemo) was most likely to be the best mode (probability = 68%). Immunotherapy + Immunotherapy + Anti-angiogenic therapy + Chemotherapy (IO + Anti-angio + Chemo) was significantly better than most other treatment modes for progression-free survival (PFS) with better objective response rate (ORR) and more obvious grade ≥3 treatment-related adverse events (TRAEs). In PD-L1-high cohort, IO + Anti-angio + Chemo seemed to be the best mode for OS, PFS, and ORR according to the ranking profiles. In PD-L1-intermediate and PD-L1-negative cohort, IO + IO + Chemo was inclined to be ranked first for prolonging OS (probability = 78%; 37%) and IO + Anti-angio + Chemo was most likely to provide best PFS (probability = 96%; 100%).

Conclusion: IO + IO + Chemo has great potential to improve the OS regardless of histology type, especially in PD-L1-intermediate and PD-L1-negative cohort. IO + Anti-angio + Chemo shows great superiority in improving the short-term survival accompanied by increasing grade ≥3 TRAEs.