First-line chemotherapy plus immune checkpoint inhibitors or bevacizumab in advanced non-squamous non-small-cell lung cancer without EGFR mutations or ALK fusions

Aim: To compare the efficacy and safety of first-line chemotherapy (Chemo) plus immune checkpoint inhibitors (ICIs) or bevacizumab (Bev) in advanced non-squamous non-small-cell lung cancer without EGFR mutations or ALK fusions. Methods: A network meta-analysis was conducted to synthesize relative treatment outcomes. Results: Chemo + ICIs is superior to Chemo + Bev in both overall survival (hazard ratio: 0.92; 95% CI: 0.88-0.96) and progression-free survival (hazard ratio: 0.93; 95% CI: 0.90-0.97), with comparable severe adverse events. However, for patients with liver metastasis, Chemo + Bev has a 59.8% probability of providing better overall survival benefit. For specific regimens, pembrolizumab + Chemo showed an absolute advantage over other regimens. Conclusion: First-line Chemo + ICIs is superior to Chemo + Bev in advanced non-squamous non-small-cell lung cancer except for patients with liver metastasis. Plain language summary Chemotherapy plus immune checkpoint inhibitors and chemotherapy plus bevacizumab were both superior to traditional chemotherapy and were recommended as the first-line treatment for advanced non-squamous non-small-cell lung cancer patients without EGFR mutations or ALK fusions. However, the efficacy and safety of these two treatment models have not been comprehensively discussed head-to-head in clinical trials. Therefore, a network meta-analysis was performed to compare efficacy between these two treatment models, especially according to different clinical characteristics, to guide decision making in clinical practice.