The efficacy and safety of anti-PD-1/PD-L1 in treatment of glioma: a single-arm meta-analysis

Yi-Fan Zeng; Xin-Yu Wei; Qi-Hao Guo; Si-Yu Chen; Sheng Deng; Zheng-Zheng Liu; Zhi-Cheng Gong; Wen-Jing Zeng

doi:10.3389/fimmu.2023.1168244

The efficacy and safety of anti-PD-1/PD-L1 in treatment of glioma: a single-arm meta-analysis

Front Immunol. 2023 Apr 14:14:1168244. doi: 10.3389/fimmu.2023.1168244. eCollection 2023.

Authors

Yi-Fan Zeng¹, Xin-Yu Wei^{2

3}, Qi-Hao Guo^{2

4}, Si-Yu Chen^{2

3}, Sheng Deng^{2

3}, Zheng-Zheng Liu⁵, Zhi-Cheng Gong^{2

3}, Wen-Jing Zeng^{2

3}

Affiliations

¹ Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.
⁵ Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

Objective: This meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in patients with glioma.

Methods: PubMed, EMBASE, Web of Science, and the Cochrane library were searched from inception to January 2023 without language restriction. Primary outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The risk of bias was assessed by subgroup analysis, sensitivity analysis, and publication bias, including funnel plot, Egger's test, and Begg's test.

Results: A total of 20 studies involving 2,321 patients were included in this meta-analysis. In the analysis of the included phase III clinical trials, the forest plot showed that PD-1/PD-L1 inhibitors did not improve the OS (HR=1.15, 95% CI: 1.03-1.29, P=0.02, I² = 14%) and PFS (HR=1.43, 95% CI: 1.03-1.99, P=0.03, I² = 87%). In the single-arm analysis, the forest plot demonstrated that the 6-month OS was 71% (95% CI: 57%-83%, I² = 92%), 1-year OS was 43% (95% CI: 33%-54%, I² = 93%), and the 2-year OS was 27% (95% CI: 13%-44%, I² = 97%). The pooled estimate of the median OS was 8.85 months (95% CI: 7.33-10.36, I² = 91%). Furthermore, the result indicated that the 6-month PFS was 28% (95% CI: 18%-40%, I² = 95%), 1-year PFS was 15% (95% CI: 8%-23%, I² = 92%), and the 18-month PFS was 10% (95% CI: 3%-20%, I² = 93%). The pooled estimate of the median PFS was 3.72 months (95% CI: 2.44-5.00, I² = 99%). For ORR, the pooled estimate of ORR was 10% (95% CI: 2%-20%, I² = 88%). We further analyzed the incidence of PD-1/PD-L1 inhibitor-related AEs, and the pooled incidence of AEs was 70% (95% CI: 58%-81%, I² = 94%). The incidence of AEs ≥ grade 3 was 19% (95% CI: 11%-30%, I² = 94%). The funnel plot for the median PFS and median OS was symmetric with no significant differences in Egger's test and Begg's test. The sensitivity analysis revealed that our results were stable and reliable.

Conclusion: The results of this meta-analysis suggest that anti-PD-1/PD-L1 therapy is relatively safe but could not prolong survival in glioma. More randomized controlled trials are needed to confirm our results.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023396057.

Keywords: PD- 1/L1; drug effect evaluation; drug safety; glioma; meta - analysis.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen*
Glioma* / drug therapy
Humans
Immune Checkpoint Inhibitors* / therapeutic use

Substances

B7-H1 Antigen
Immune Checkpoint Inhibitors

Grants and funding

This study was supported by the National Natural Science Foundation of China (No.81903663), and the Hunan Provincial Natural Science Foundation of China (No. 2020JJ5944).