Trial reportJournal of hepatology2020
Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma.
Trial report in Journal of hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01658878 (A Phase 1/2, Dose-escalation, Open-label, Non-comparative Study of Nivolumab or Nivolumab in Combination With Ipilimumab in Advanced Hepatocellular Carcinoma Subjects With or Without Chronic Viral Hepatitis; and a Randomized, Open-label Study of Nivolumab vs Sorafenib in Advanced Hepatocellular Carcinoma Subjects Who Are Naive to Systemic Therapy), which is not on this map. Cited by 269 papers, 4 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.
A Phase 1/2, Dose-escalation, Open-label, Non-comparative Study of Nivolumab or Nivolumab in Combination With Ipilimumab in Advanced Hepatocellular Carcinoma Subjects With or Without Chronic Viral Hepatitis; and a Randomized, Open-label Study of Nivolumab vs Sorafenib in Advanced Hepatocellular Carcinoma Subjects Who Are Naive to Systemic Therapy
Who cites it
269 citing papers in PubMed, 4 syntheses or guidelines pooled it, 408 citations in OpenAlex.
- Pooled it
- Neoadjuvant Immune Checkpoint Inhibitors in hepatocellular carcinoma: a meta-analysis and systematic review.Frontiers in immunology · 2024Pooled it
- The predictive value of PD-L1 expression in patients with advanced hepatocellular carcinoma treated with PD-1/PD-L1 inhibitors: A systematic review and meta-analysis.Cancer medicine · 2023Pooled it
- Development and validation of prognostic risk prediction models for hepatocellular carcinoma patients treated with immune checkpoint inhibitors based on a systematic review and meta-analysis of 47 cohorts.Frontiers in immunology · 2023Pooled it
- Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial.Nature medicine · 2025Trial
- Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial.Nature medicine · 2024Trial
- Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab.Journal for immunotherapy of cancer · 2024Trial
- Artificial intelligence and personalised medicine in liver cancer.Journal of hepatology · 2026Review
- scRNA-seq and bulk RNA-seq reveal the characteristics of macrophage copper metabolism and establish a risk signature in hepatocellular carcinoma.Translational cancer research · 2026Article
- Multidimensional analysis of tumour immune microenvironment in HCC: prognostic significance and implications for immunotherapy.Cancer immunology, immunotherapy : CII · 2026Article
- Polysaccharides: Natural candidates for targeting immunometabolic regulation in hepatocellular carcinoma (Review).Molecular medicine reports · 2026Review
- Integrative analysis of SEC13: a prognostic predictor and immunotherapeutic target.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Targeting SMYD2 improves immunotherapy response in experimental hepatocellular carcinoma.Molecular therapy. Oncology · 2026Article
- HBV-driven expansion of CXCR6Innovation (Cambridge (Mass.)) · 2026Article
- Breakthroughs in HBV-related HCC Therapy: The Unmatched Potential of Immune Checkpoint Inhibitors.Current treatment options in oncology · 2026Review
- Histone methyl-transferase G9a inhibition boosts the efficacy of immune checkpoint inhibitors in experimental hepatocellular carcinoma.Cell reports. Medicine · 2026Article
- Combining External Beam Radiotherapy and Immunotherapy for the Treatment of Hepatocellular Carcinoma.Current oncology (Toronto, Ont.) · 2026Review
- Review
- Clinical applications of immunogenomics in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
209 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 10 institutions in 6 countries.
Funding
Abstract
BACKGROUND &
aimsNivolumab, a programmed death (PD)-1 (PD-1) inhibitor, led to durable responses, manageable safety, and increased survival in patients with advanced hepatocellular carcinoma (HCC). In our retrospective analysis, we studied the immunobiology and potential associations between biomarkers and outcomes with nivolumab in HCC.
methodsFresh and archival tumour samples from dose-escalation and dose-expansion phases of the CheckMate 040 trial were analysed by immunohistochemistry and RNA sequencing to assess several inflammatory gene expression signatures, including CD274 (PD-ligand 1 [PD-L1]), CD8A, LAG3, and STAT1. Biomarkers were assessed for association with clinical outcomes (best overall response by blinded independent central review per RECIST v1.1 and overall survival [OS]).
resultsComplete or partial tumour responses were observed in PD-L1-positive and PD-L1-negative patients treated with nivolumab monotherapy. Median OS was 28.1 (95% CI 18.2-n.a.) vs. 16.6 months (95% CI 14.2-20.2) for patients with tumour PD-L1 ≥1% vs. <1% (p = 0.03). Increased CD3 and CD8 showed a non-significant trend towards improved OS (both p = 0.08), and macrophage markers were not associated with OS. Tumour PD-1 and PD-L1 expression were associated with improved OS (p = 0.05 and p = 0.03, respectively). An inflammatory gene signature consisting of 4 genes was associated with improved objective response rate (p = 0.05) and OS (p = 0.01).
conclusionsPD-1 and PD-L1 expression, biomarkers of inflammation, and inflammatory gene signatures trended with improved survival and response. While further confirmation within a larger phase III trial is needed to evaluate predictive value of these biomarkers, these exploratory analyses suggest that anti-tumour immune response may play a role in the treatment benefit of nivolumab in HCC. LAY SUMMARY: Certain tests may be used to provide a picture of how a tumour is escaping the immune system, allowing it to continue to grow and create more tumours. Therapies such as nivolumab are designed to help the immune system fight the tumour. These tests may be used to determine how effective such therapies will be in the treatment of advanced liver cancer. NCT NUMBER: NCT01658878.
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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.