The benefit and risk of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small-cell lung cancer: a systematic review and single-arm meta-analysis of prospective clinical trials

Abstract

Background: Previous studies revealed that Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents had extensive anti-tumor activities. However, almost all studies on the efficacy and safety of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small cell lung cancer are non-randomized controlled trials with small sample sizes, which might lead to a lack of effective metrics to assess the effectiveness and safety of the therapeutic regimen. Here, this meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small cell lung cancer.

Methods: A single-arm meta-analysis was performed, and published literature from PubMed, Web of Science and Embase databases as of January 13, 2023, was systematically retrieved. We used the Cochrane risk of bias tool and methodological index for non-randomized studies (MINORS) Methodological items to evaluate the quality of eligible clinical trials. Outcomes including overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted for further analysis. The random effect model is used to calculate the pooled parameters.

Results: 19 studies (16 were non-comparative single-arm clinical trials and 3 were randomized controlled trials) were enrolled in this meta-analysis. In terms of tumor response, the pooled ORR and DCR were 22.4% (95% CI, 16.6-28.1%) and 76.8% (95% CI, 72.6-81.1%), respectively. With regard to survival analysis, the pooled PFS and OS were 5.20 (95% CI, 4.46-5.93) months and 14.09 (95% CI, 13.20-14.97) months, respectively. The pooled grade ≥3 adverse effect (AE) rate was 47.6% (95% CI, 33.1-62.0%).

Conclusion: PD-1/PD-L1 inhibitors plus anti-angiogenic agents has promising efficacy and safety as second or later-line treatment in patients with advanced non-small cell lung cancer.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023407559.

Keywords: PD-1/PD-L1 inhibitors; advanced non-small cell lung cancer; anti-angiogenic agents; meta-analysis; second or later-line therapy.

Figure 1

Flow chart of the single-arm meta-analysis.

Figure 2

Forest plot about the pooled results of ORR (A) and DCR (B).

Figure 3

Coefplot of the results of meta-regression of ORR (A) and DCR (B).

Figure 4

Subgroup analysis of ORR in immunotherapy inhibitor (A), anti-angiogenic agent (B), EGFR mutation (C) and whether or not to combine chemotherapy (D).

Figure 5

Subgroup analysis of DCR in immunotherapy inhibitor (A), anti-angiogenic agent (B), EGFR mutation (C) and whether or not to combine chemotherapy (D).

Figure 6

Forest plot about the pooled results of OS (A) and PFS (B).

Figure 7

Coefplot of the results of meta-regression of PFS (A) and AE (B).

Figure 8

Subgroup analysis of PFS in immunotherapy inhibitor (A), anti-angiogenic agent (B), EGFR mutation (C) and whether or not to combine chemotherapy (D).

Figure 9

Forest plot about the pooled results of AE.

Figure 10

Subgroup analysis of AE in immunotherapy inhibitor (A), anti-angiogenic agent (B), EGFR mutation (C) and whether or not to combine chemotherapy (D).