Impact of treatment timing and sequence of immune checkpoint inhibitors and anti-angiogenic agents for advanced non-small cell lung cancer: A systematic review and meta-analysis

•Clinical effects of ICI and AA therapy are evaluated in comparison with either monotherapy for advanced non-small cell lung cancer.•ICI and AA therapy showed a higher objective response rate than either monotherapy.•AA administered concomitantly or immediately after ICI can provide favorable survival benefits compared to either monotherapy.•ICI administered immediately after AA may show no survival benefits compared to ICI monotherapy. Several studies have demonstrated that anti-angiogenic agents (AAs) have the ability to regulate immune-related cells in the tumor microenvironment and may affect the clinical effect of immune checkpoint inhibitors (ICIs). Therefore, we investigated the drug interaction between ICI and AA for advanced non-small cell lung cancer (NSCLC). We systematically searched PubMed-MEDLINE, Embase-Scopus, and ISI Web of Science before August 23, 2021. ICI and AA therapy included the concomitant and sequential use of ICIs and AAs. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of patients who received ICI and AA therapy were evaluated and compared to those of patients who received either monotherapy. Subgroup analyses were performed to clarify the cause of heterogeneity; the timing and sequence of ICI and AA administration were predefined as the subgroups. Thirteen studies involving 2414 patients were included in the meta-analysis. ICI and AA therapy had significantly higher ORR than either monotherapy (OR [95% CI]: 0.61 [0.50–0.74]; p