Abstract
Purpose
Programmed death ligand 1(PD-L1)/programmed cell death-1(PD-1) inhibitors have shown promising efficacy in unresectable patients with advanced hepatocellular carcinoma (HCC), but the results are not consistent. Our goal was to evaluate the safety and efficacy of PD-L1/PD-1 inhibitors or plus anti-CTLA-4 antibody or anti-VEGF agents for the treatment of unresectable HCC.
Methods
Cochrane library, Embase, and PubMed were searched till August 2021. Data on progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and disease control rate (DCR) were pooled and analyzed by Stata14 software.
Results
Thirteen prospective trials with 2,386 HCC patients were included. Pooled analysis estimated an ORR of about 0.21 (95% CI = 0.18–0.25) and a DCR of 0.59 (95% CI = 0.52–0.65) for anti-PD-1/PD-L1 therapy. Summary PFS was 4.19 (95% CI = 3.31–5.18) months and summary OS was 13.23 (95% CI = 12.06–14.41) months. After using PD-L1/PD-1 inhibitors plus anti-VEGF agents, ORR was 0.26 (95% CI = 0.20–0.33), DCR was 0.75 (95% CI = 0.69–0.81) and PFS was 6.2 (95% CI = 4.61–7.78) months. PD-L1/PD-1 inhibitors plus anti-CTLA-4 antibody therapy achieved an ORR of 0.23 (95% CI = 0.14–0.33), an DCR of 0.44 (95% CI = 0.39–0.50) and a PFS of 1.88 (95% CI = 1.51–2.26).
Conclusions
PD-L1/PD-1 inhibitors were effective and tolerable in patients with advanced HCC. Furthermore, compared with anti-PD-1/PD-L1 monotherapy, PD-L1/PD-1 inhibitors plus anti-VEGF agents resulted in more clinical improvements in ORR, DCR, and PFS.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- PD-1:
-
Programmed cell death-1
- PD-L1:
-
Programmed death ligand 1
- HCC:
-
Hepatocellular carcinoma
- ORR:
-
Objective response rate
- DCR:
-
Disease control rate
- OS:
-
Overall survival
- PFS:
-
Progression-free survival
- TACE:
-
Transcatheter arterial chemoembolization
- ICIs:
-
Immune checkpoint inhibitors
- TrAEs:
-
Treatment-related adverse events
- NSCLC:
-
Non-small cell lung cancer
- UC:
-
Urothelial cancer
- MM:
-
Metastatic melanoma
- HNSCC:
-
Head and neck squamous cell carcinoma
- ImAE:
-
Immune-mediated adverse events
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WW and YZ carried out the studies, participated in collecting data, and drafted the manuscript. WW and HZ performed the statistical analysis and participated in its design. WW and YSC participated in the acquisition, analysis, or interpretation of data and drafted the manuscript. All authors read and approved the final manuscript.
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Wen, W., Zhang, Y., Zhang, H. et al. Clinical outcomes of PD-1/PD-L1 inhibitors in patients with advanced hepatocellular carcinoma: a systematic review and meta-analysis. J Cancer Res Clin Oncol 149, 969–978 (2023). https://doi.org/10.1007/s00432-022-04057-3
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DOI: https://doi.org/10.1007/s00432-022-04057-3