Effectiveness of PD1/PD‑L1 combined with anti‑angiogenic drugs in patients with advanced nonsmall cell lung cancer: A systematic review and meta‑analysis

Protein‑1 (PD‑1) and programmed cell death 1 ligand 1 (PD‑L1) therapy have become an important treatment approach for patients with advanced nonsmall cell lung cancer (NSCLC), but primary or secondary resistance remains a challenge for some patients. PD‑1/PD‑L1 combined with anti‑angiogenic drugs (AAs) in NSCLC patients have potential synergistic effects, and the survival benefit may vary based on a treatment order. To investigate the efficacy of PD‑1/PD‑L1 combined with AAs as the treatment for patients with advanced NSCLC.

We comprehensively searched EMBASE, PubMed, Web of Science, CNKI, VIP, and Wanfang databases from January 2017 to September 2022. The Cochrane risk bias tool evaluated the quality of included randomized clinical trials. Newcastle‑Ottawa‑Scale score was used to evaluate the quality of retrospective studies. Publication bias was evaluated by funnel plot, Begg’s test, and Egger’s test.

Seventeen articles were finally selected, involving 5182 patients. Meta‑analysis results showed that PD1/PD‑L1 combined with AAs therapy significantly improved progression‑free survival (PFS) (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.50–0.75, P < 0.00001), overall survival (OS) (HR = 0.79, 95% CI: 0.71–0.88, P < 0.00001), and objective response rate (ORR) (risk ratio = 0.88, 95% CI: 0.81–0.96, P = 0.004), with the statistically significant difference. The sensitivity analysis demonstrated the robustness of the PFS, ORR, and OS.

The combination of PD‑1/PD‑L1 inhibitors with AAs in treating advanced patients has exhibited notable therapeutic advantages when contrasted with monotherapy. Specifically, the administration of PD‑1/PD‑L1 inhibitors in conjunction with AAs, or sequential treatment involving PD‑1/PD‑L1 followed by AAs, has shown enhanced therapeutic efficacy in this patient population.