Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis
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Xiaohui Wang1,2,*, Zhengqiang Bao1,2,*, Xiaoju Zhang3,*, Fei Li1, Tianwen Lai1, Chao Cao1, Zhihua Chen1, Wen Li1, Huahao Shen1,4 and Songmin Ying1,2
1 Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou, China
2 Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, China
3 Department of Respiratory Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, China
4 State Key Laboratory of Respiratory Diseases, Guangzhou, China
* These authors have contributed equally to this manuscript
Songmin Ying, email:
Huahao Shen, email:
Keywords: PD-1, PD-L1, nivolumab, pembrolizumab, cancer
Received: August 12, 2016 Accepted: March 01, 2017 Published: May 31, 2017
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) 2.92; 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.
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