SynthesisBMC cancer2023
Efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the unresectable hepatocellular carcinoma and the benefit for hepatitis B virus etiology subgroup: a systematic review and meta-analysis of randomized controlled trials.
Synthesis in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 3 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- First-line immunotherapy for advanced hepatocellular carcinoma: a network meta-analysis of randomized trials with overall and HBV/HCV-stratified efficacy and safety.Frontiers in immunology · 2026Pooled it
- Survival benefits of different immunotherapies for hepatocellular carcinoma: a meta-analysis highlighting age, gender, etiology, and tumor burden.Frontiers in immunology · 2025Pooled it
- Hepatotoxicity of ICI monotherapy or combination therapy in HCC: A systematic review and meta-analysis.PloS one · 2025Pooled it
- Breakthroughs in HBV-related HCC Therapy: The Unmatched Potential of Immune Checkpoint Inhibitors.Current treatment options in oncology · 2026Review
- Immunotherapy in hepatocellular carcinoma: translating mechanistic insights into clinical advances.Clinical and experimental medicine · 2026Review
- Beyond viral suppression: combining PEG-interferon with novel immunotherapies for functional cure of chronic hepatitis B.Frontiers in cellular and infection microbiology · 2026Review
- The interplay between hepatitis B virus and antitumor drugs in the treatment of hepatocellular carcinoma.Clinical and experimental medicine · 2025Review
- Predicting the occurrence of liver injury induced by immune checkpoint inhibitors in hepatocellular carcinoma patients: a retrospective analysis.BMC cancer · 2025Article
- Targeting YTHDF2 with pH-responsive siRNA nanoparticles suppresses MYC m6A modification and restores antitumor immunity in hepatocellular carcinoma.Journal of nanobiotechnology · 2025Article
- Up-regulated programmed cell death protein-1/its ligand 1 expression promotes metabolic dysfunction-associated steatotic liver disease malignant progression.World journal of gastrointestinal oncology · 2025Article
- Immune checkpoint inhibitors plus anti-angiogenesis in patients with resected high-risk hepatitis B virus-associated hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Article
- PD‑1/PD‑L1 immune checkpoint in bone and soft tissue tumors (Review).Molecular and clinical oncology · 2025Review
- Efficacy and safety of PD-1/PD-L1 inhibitors combined with tyrosine kinase inhibitors as first-line treatment for hepatocellular carcinoma: a meta-analysis and trial sequential analysis of randomized controlled trials.Frontiers in pharmacology · 2025Article
- The current status and future of targeted-immune combination for hepatocellular carcinoma.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, worldwide. The predominant causative factor for HCC is hepatitis B virus (HBV) infection. We conducted a meta-analysis to estimate the efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the first-line treatment of the unresectable HCC and to evaluate the benefits of different geographic regions and etiology stratifications.
methodsRandomized clinical trials published up to 12th November 2022 were searched by online databases. Moreover, effects of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were extracted from included studies. Pooled odds ratio (OR) and 95% CI for objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) were calculated.
resultsA total of 3057 patients from five phase III randomized clinical trials were collected and reviewed for this meta-analysis. The pooled HR of OS (HR = 0.71; 95% CI: 0.60-0.85) and PFS (HR = 0.64; 95% CI: 0.53-0.77) demonstrated significantly better benefit in PD-1/PD-L1 inhibitors combination group than targeted monotherapy to treat unresectable HCC. In addition, combination therapy showed better ORR and DCR, with ORs of 3.29 (95% CI: 1.92-5.62) and 1.88 (95% CI: 1.35-2.61), respectively. The subgroup analysis indicated that PD-1/PD-L1 inhibitors combination therapy was significantly superior to anti-angiogenic monotherapy for HBV-related HCC in terms of OS (HR = 0.64; 95% CI: 0.55-0.74) and PFS (HR = 0.53; 95% CI:0.47-0.59), while there was no significant difference in patients with HCV (OS, HR = 0.81, p = 0.1) or non-viral (OS, HR = 0.91, p = 0.37; PFS, HR = 0.77, p = 0.05).
conclusionsMeta-analysis revealed for the first-time that PD-1/PD-L1 inhibitors combination therapy for unresectable HCC was associated with better clinical outcomes than anti-angiogenic monotherapy, especially for HBV infection and Asian population.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.