Trial reportThe oncologist2017
Phase II Study of First-Line Trebananib Plus Sorafenib in Patients with Advanced Hepatocellular Carcinoma.
Trial report in The oncologist, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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
17 citing papers in PubMed, 22 citations in OpenAlex.
- A novel prognostic model based on MVIRGs identifies ANGPT2 as a key target driving the malignant progression of HCC.Biological procedures online · 2026Article
- Prevalence of gastrointestinal side effects in hepatocellular carcinoma patients receiving sorafenib: a meta-analysis of 136 studies and 14,416 patients.Therapeutic advances in medical oncology · 2026Article
- Denoised recurrence label-based deep learning for prediction of postoperative recurrence risk and sorafenib response in HCC.BMC medicine · 2025Article
- Aberrant angiogenic signaling in HCC: therapeutic targeting and drug resistance.Frontiers in oncology · 2025Review
- Angiogenesis and Hepatocellular Carcinoma: From Molecular Mechanisms to Systemic Therapies.Medicina (Kaunas, Lithuania) · 2023Review
- Novel Drugs with High Efficacy against Tumor Angiogenesis.International journal of molecular sciences · 2022Review
- Antiangiogenic Drugs in NASH: Evidence of a Possible New Therapeutic Approach.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Advances of Targeted Therapy for Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- Review
- Recent progress in treatment of hepatocellular carcinoma.American journal of cancer research · 2020Review
- Is the era of sorafenib over? A review of the literature.Therapeutic advances in medical oncology · 2020Review
- Review
- Tie-ing Up Angiogenesis to Treat Nonalcoholic Steatohepatitis.Hepatology (Baltimore, Md.) · 2019Article
- Angiopoietin-1 and Angiopoietin-2 Inhibitors: Clinical Development.Current oncology reports · 2019Review
- Clinical and prognostic significance of circulating levels of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma.Oncotarget · 2018Article
- Anti-angiogenic agents for the treatment of solid tumors: Potential pathways, therapy and current strategies - A review.Journal of advanced research · 2017Review
- Angiogenesis Inhibitors for the Treatment of Hepatocellular Carcinoma.Frontiers in pharmacology · 2016Review
Corrections and comments
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Authors and funding
16 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
lessons learnedTrebananib leveraging anti-angiogenic mechanism that is distinct from the classic sorafenib anti-vascular endothelial growth factor inhibition did not demonstrate improved progression-free survival at 4 months in patients with advanced hepatocellular carcinoma (HCC).In support of previously reported high Ang-2 levels' association with poor outcome in HCC for patients, trebananib treatment with lower baseline Ang-2 at study entry was associated with improved overall survival to 22 months and may suggest future studies to be performed within the context of low baseline Ang-2.
backgroundAng-1 and Ang-2 are angiopoietins thought to promote neovascularization via activation of the Tie-2 angiopoietin receptor. Trebananib sequesters Ang-1 and Ang-2, preventing interaction with the Tie-2 receptor. Trebananib plus sorafenib combination has acceptable toxicity. Elevated Ang-2 levels are associated with poor prognosis in hepatocellular carcinoma (HCC).
methodsPatients with HCC, Eastern Cooperative Oncology Group ≤2, and Childs-Pugh A received IV trebananib at 10 mg/kg or 15 mg/kg weekly plus sorafenib 400 mg orally twice daily. The study was planned for ≥78% progression-free survival (PFS) rate at 4 months relative to 62% for sorafenib historical control (power = 80% α = 0.20). Secondary endpoints included safety, tolerability, overall survival (OS), and multiple biomarkers, including serum Ang-2.
resultsThirty patients were enrolled sequentially in each of the two nonrandomized cohorts. Demographics were comparable between the two arms and the historical controls. PFS rates at 4 months were 57% and 54% on the 10 mg/kg and 15 mg/kg trebananib cohorts, respectively. Median OS was 17 and 11 months, respectively. Grade 3 and above events noted in ≥10% of patients included fatigue, hypertension, diarrhea, liver failure, palmar-plantar erythrodysesthesia syndrome, dyspnea, and hypophosphatemia. One death was due to hepatic failure. Serum Ang-2 dichotomized at the median was associated with improved OS in both cohorts.
conclusionThere was no improvement in PFS rate at 4 months in either cohort, when compared with sorafenib historical control.
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