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.