Clinical benefits of PD-1/PD-L1 inhibitors in advanced hepatocellular carcinoma: a systematic review and meta-analysis
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ORIGINAL ARTICLE
Clinical benefits of PD‑1/PD‑L1 inhibitors in advanced hepatocellular carcinoma: a systematic review and meta‑analysis Quan Rao1 · Min Li2 · Wei Xu1 · Kai Pang1 · XiaoBo Guo3 · Dong Wang1 · Jun Liu1 · Wei Guo1 · ZhongTao Zhang1 Received: 5 March 2020 / Accepted: 6 June 2020 © Asian Pacific Association for the Study of the Liver 2020
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. Keywords PD-1 · PD-L1 · Monoclonal antibody · Nivolumab · Pembrolizumab · Anti-VEGF agent · Objective response rate · Disease control rate · Overall survival · Progression-free survival · Adverse event · Meta-analysis
Introduction Quan Rao and Min Li contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12072-020-10064-8) contains s
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