Efficacy and safety of anlotinib combined with PD-1/PD-L1 inhibitors in malignant solid tumors: a meta-analysis and network meta-analysis

Objective To evaluate the efficacy and safety of anlotinib combined with programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in the treatment of malignant solid tumors. Methods PubMed, Web of Science, Embase, and Cochrane Library databases were searched to collect randomized controlled trials (RCTs), cohort studies, and single-arm studies comparing anlotinib combined with PD-1/PD-L1 inhibitors (combination group) against other therapies (control group) for the treatment of malignant solid tumors. The search period spanned from the inception of each database to November 2025. Results 26 studies involving 3,263 patients were identified. The Objective Response Rate (ORR) in the combination group was 57% (95% CI: 47%-67%), with a Disease Control Rate (DCR) of 90% (95% CI: 84%-93%). The incidence of adverse reactions included fatigue (RR = 1.196, 95% CI: 1.024-1.396) and hypoalbuminemia (RR = 1.336, 95% CI: 1.121-1.593). Compared with the control group, the combination group significantly improved ORR in malignant solid tumors (RR = 1.70, 95% CI: 1.29-2.25, P ≤ 0.0001), DCR (RR = 1.08, 95% CI: 1.02-1.14, P = 0.009), Overall Survival (OS) (HR = 0.64, 95% CI: 0.54-0.76, P ≤ 0.001), and Progression Free Survival (PFS) (HR = 0.48, 95% CI: 0.39-0.59, P ≤ 0.001). The incidence of hypoalbuminemia was higher in the combination group than in the control group. Results from a network meta-analysis indicated superior efficacy for the combination of anlotinib and TQB2450. Conclusion Anlotinib combined with PD-1/PD-L1 inhibitors demonstrates significant efficacy in treating multiple tumor types. The combination of anlotinib and TQB2450 offers advantages, but attention should be paid to the occurrence of hypoproteinemia.