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Clinical benefits of PD-1/PD-L1 inhibitors in advanced hepatocellular carcinoma: a systematic review and meta-analysis

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Abstract

Background

Significant improvement of objective response rate and overall survival period has been achieved in several types of solid tumors by treatment with PD-1/PD-L1 inhibitors, which shed some light on hepatocellular carcinoma (HCC). Currently, a number of clinical trials concerning the application of checkpoint inhibitors in HCC are ongoing, some of which have shown favorable expectations. Hereby, we conducted a meta-analysis of existing studies to reveal the efficacy and safety of checkpoint inhibitors in advanced HCC.

Methods

Medline, Embase, Cochrane Library, and Web of Science were searched from inception to January 31, 2020. The clinical trials reporting the efficacy of PD-1/PD-L1 inhibitors in advanced HCC patients were eligible. Overall results of complete response (CR), partial response (PR), stable disease (SD), progression of disease (PD), objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS) and rate of adverse events (AE) with their 95% confidence intervals (95%CI) were calculated as the primary focus of the meta-analysis. Subgroup analyses were conducted primarily according to the categories of PD-1 inhibitor or PD-L1 inhibitor and combination therapy or monotherapy. In addition, pooled results of PD-1/PD-L1 monoclonal antibodies (mAb) combining with anti-VEGF agents were calculated separately.

Results

A total of 20 studies with 1232 patients were included. The overall CR, PR and SD rate were 0.01 (95% CI 0.01–0.03), 0.17 (95% CI 0.14–0.22) and 0.39 (95% CI 0.34–0.43), respectively. The overall ORR and DCR were 0.20 (95% CI 0.16–0.24) and 0.60 (95% CI 0.54–0.67), respectively. The overall PFS and OS were 3.58 months (95% CI 2.65–4.50) and 12.24 months (95% CI 10.48–14.00), respectively. For patients treated with PD-1/PD-L1 mAb combing with anti-VEGF agent, ORR was 29% (95% CI 0.15–0.43) and DCR was 77% (95% CI 0.70–0.84). For all included studies, the overall rate of AE was 0.63 (95% CI 0.45–0.78) and serious adverse events (SAE) was 0.11 (95% CI 0.06–0.22).

Conclusions

PD-1/PD-L1 inhibitors showed favorable outcomes concerning response rates and survival periods in advanced HCC. Updated results from high-quality clinical trials are expected to validate these findings.

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Acknowledgements

This study was supported by National Key Technologies R&D Program of China (no. 2017YFC0110904), National Key Technologies R&D Program of China (no. 2017YFC0110904), National Natural Science Foundation of China (no. 81800577), and Beijing Natural Science Foundation (no. 7202033).

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Author notes

  1. Quan Rao and Min Li contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China

    Quan Rao, Wei Xu, Kai Pang, Dong Wang, Jun Liu, Wei Guo & ZhongTao Zhang

  2. Clinical Epidemiology and EBM Unit, National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China

    Min Li

  3. Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China

    XiaoBo Guo

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  1. Quan Rao
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  2. Min Li
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Contributions

ZTZ: study design, and manuscript writing, and statistical analysis. WG: study design, manuscript writing, and finalizing. QR: study design, manuscript writing, literature searching, data abstraction, and statistical analysis. ML: manuscript writing and statistical analysis. WX: literature review, and manuscript writing and reviewing. DW: study design, literature search, and review. KP: literature review, and manuscript writing and reviewing. XBG: manuscript writing and reviewing.

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Correspondence to Wei Guo or ZhongTao Zhang.

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Rao, Q., Li, M., Xu, W. et al. Clinical benefits of PD-1/PD-L1 inhibitors in advanced hepatocellular carcinoma: a systematic review and meta-analysis. Hepatol Int 14, 765–775 (2020). https://doi.org/10.1007/s12072-020-10064-8

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