PD-1/PD-L1 inhibitor plus chemotherapy versus bevacizumab plus chemotherapy in first-line treatment for non-squamous non-small-cell lung cancer

Anti-PD-1)/programmed cell death-ligand 1 (PD-L1) antibody plus platinum-based chemotherapy (PBC) has replaced PBC as first-line treatment for patients with non-squamous (sq) non-small cell lung cancer (NSCLC) lacking targetable driver mutations. However, few studies have directly compared immune checkpoint inhibitor (ICI) plus chemotherapy with bevacizumab plus chemotherapy (beva +chemo) in this setting. Herein, we conducted an indirect comparison for anti-PD-1/PD-L1 antibody plus chemotherapy (ICI +chemo) versus beva +chemo in non-sq NSCLC using the frequentist methods. The main outcomes analyzed include progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Data were subtracted from randomized trials comparing ICI +chemo or beva +chemo against PBC. Fourteen trials involving 6165 patients were included. Direct meta-analyses showed that both ICI +chemo (PFS: HR 0.58, OS: HR 0.73, ORR: relative risk (RR) 1.66) and beva +chemo (PFS: HR 0.74, OS: HR 0.89, ORR: RR 1.62) improved clinical outcomes compared with PBC. Indirect comparison showed that ICI +chemo reduced the risk of disease progression (HR 0.78, 95% CI 0.60 to 1.00) and death (HR 0.82, 95% CI 0.71 to 0.94) compared with beva +chemo. The PFS benefits with ICI +chemo over beva +chemo were non-significant in those with negative PD-L1 expression and non-smokers. In conclusion, ICI +chemo is superior to beva +chemo in first-line treatment for non-sq NSCLC.