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Review
. 2017 May 31;8(35):59901-59914.
doi: 10.18632/oncotarget.18316. eCollection 2017 Aug 29.

Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis

Xiaohui Wang #  1   2 , Zhengqiang Bao #  1   2 , Xiaoju Zhang #  3 , Fei Li  1 , Tianwen Lai  1 , Chao Cao  1 , Zhihua Chen  1 , Wen Li  1 , Huahao Shen  1   4 , Songmin Ying  1   2
Affiliations
Review

Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis

Xiaohui Wang et al. Oncotarget. .

Abstract

Background: PD-1/PD-L1 inhibitors have been implicated as potentially effective anti-cancer therapies. Some clinical randomized controlled trials (RCTs) have been completed for a variety of PD-1/PD-L1 inhibitors to treat various malignancies, and more RCTs are still under way. We carried out this systematic meta-analysis to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors.

Methods: We searched PubMed, EMBASE, clinical trial registers, conference reports, and related reviews. Eligible RCTs that compared PD-1/PD-L1 inhibitors with other chemotherapy agents or placebo in solid tumor patients were included. For each RCT, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), stable disease rate (SDR), progressive disease rate (PDR), and adverse events (AEs) were pooled for meta-analysis.

Findings: Based on an analysis of 10 eligible RCTs, PD-1/PD-L1 inhibitors were found to significantly improve PFS (Hazard ratio (HR), 0.65; 95% confidence interval (CI) 0.53 to 0.79, P<0.001), OS (HR, 0.69; 95%CI 0.62 to 0.76, P<0.001), and ORR (Risk Ratio (RR) 292; 95% confidence interval (CI) 2.06 to 4.15, P<0.00001) in all populations, including melanoma and NSCLC subgroups. However, they failed to increase the DCR of cancer patients (RR 1.15; 95%CI 0.91 to 1.45, P=0.25). Furthermore, less AEs were observed in the PD-1/PD-L1 inhibitor groups than the control groups.

Interpretation: PD-1 inhibitors are more effective for improving the PFS, OS, and ORR of cancer patients with little toxicity, despite having little effect on increasing of the DCR.

Keywords: PD-1; PD-L1; cancer; nivolumab; pembrolizumab.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest in this work.

Figures

Figure 1
Figure 1. The process of literature search and eligible trials selection
N: the number of studies.
Figure 2
Figure 2
A. Forest plots of the pooled Hazard ratios (HRs) of Progressive-free survival (PFS) PFS in overall population. B. Forest plots of the pooled Hazard ratios (HRs) of Overall survival in overall population.
Figure 3
Figure 3. Subgroup analysis of cancer types
A. Forest plots of the pooled Relative Risk (RR) of objective response rate (ORR); B. Forest plots of the pooled Relative Risk (RR) of disease control rate (DCR).
Figure 4
Figure 4
A. Forest plots of the pooled Relative Risk (RR) of stable disease rate (SDR) and B. Forest plots of the pooled Relative Risk (RR) progressive disease rate (PDR).
Figure 5
Figure 5
A. Forest plots of the pooled Relative Risk (RR) of objective response rate (ORR) in Subgroup analysis of nivolumab and pembrolizumab.; B. Forest plots of the pooled Relative Risk (RR) of disease control rate (DCR) in Subgroup analysis of nivolumab and pembrolizumab.
Figure 6
Figure 6
A. Relative Risks (RR) of common adverse events of all grades. B. Relative Risks (RR) of adverse events of grade ≥ 3.
Figure 7
Figure 7
A. Sensitivity analysis of enrolled studies on progression-free survival (PFS). B. Sensitivity analysis of enrolled studies on objective response rate (ORR). C. Sensitivity analysis of enrolled studies on stable disease rate (SDR). D. Sensitivity analysis of enrolled studies on disease control rate (DCR).
Figure 8
Figure 8
A. Funnel plot of publication bias on progressive-free survival (PFS). B. Funnel plot of publication bias on objective response rate (ORR). C. Funnel plot of publication bias on stable disease rate (SDR). D. Funnel plot of publication bias on disease control rate (DCR).
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