ArticleThe oncologist2020
A Phase I Trial of Trametinib in Combination with Sorafenib in Patients with Advanced Hepatocellular Cancer.
Article in The oncologist, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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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
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Metabolic cell death in cancer: mechanisms and therapeutic potential.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- The efficacy and safety of different systemic combination therapies on advanced hepatocellular carcinoma: a systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications.Biochemistry and biophysics reports · 2026Review
- 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
- Integration of Whole-Genome Sequencing Analysis with Unique Patient-Derived Models Reveals Clinically Relevant Drug Targets in TFCP2 Fusion-Defined Rhabdomyosarcoma.Molecular cancer therapeutics · 2025Article
- PathSynergy: a deep learning model for predicting drug synergy in liver cancer.Briefings in bioinformatics · 2025Article
- Revolutionizing cancer treatment: the rise of personalized immunotherapies.Discover oncology · 2024Review
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- BRAFScience advances · 2023Article
- MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas.Nature communications · 2023Article
- Loss of TP53 cooperates with c-MET overexpression to drive hepatocarcinogenesis.Cell death & disease · 2023Article
- Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact.Cancers · 2022Review
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Identification of Context-Specific Fitness Genes Associated With Metabolic Rearrangements for Prognosis and Potential Treatment Targets for Liver Cancer.Frontiers in genetics · 2022Article
- The interactions between integrin αInternational journal of biological sciences · 2022Article
- Using predictive machine learning models for drug response simulation by calibrating patient-specific pathway signatures.NPJ systems biology and applications · 2021Article
- Emerging treatment modalities for systemic therapy in hepatocellular carcinoma.Biomarker research · 2021Review
- Emerging mechanisms and targeted therapy of ferroptosis in cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
lessons learnedThe combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy. Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily. The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.
backgroundThe RAS/RAF/MEK/ERK signaling pathway is associated with proliferation and progression of hepatocellular carcinoma (HCC). Preclinical data suggest that paradoxical activation of the MAPK pathway may be one of the resistance mechanisms of sorafenib; therefore, we evaluated trametinib plus sorafenib in HCC.
methodsThis was a phase I study with a 3+3 design in patients with treatment-naïve advanced HCC. The primary objective was safety and tolerability. The secondary objective was clinical efficacy.
resultsA total of 17 patients were treated with three different doses of trametinib and sorafenib. Two patients experienced dose-limiting toxicity, including grade 4 hypertension and grade 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin over 7 days. Maximum tolerated dose was trametinib 1.5 mg daily and sorafenib 200 mg twice a day. The most common grade 3/4 treatment-related adverse events were elevated AST (37%) and hypertension (24%). Among 11 evaluable patients, 7 (63.6%) had stable disease with no objective response. The median progression-free survival (PFS) and overall survival (OS) were 3.7 and 7.8 months, respectively. Phosphorylated-ERK was evaluated as a pharmacodynamic marker, and sorafenib plus trametinib inhibited phosphorylated-ERK up to 98.1% (median: 81.2%) in peripheral blood mononuclear cells.
conclusionTrametinib and sorafenib can be safely administered up to trametinib 1.5 mg daily and sorafenib 200 mg twice a day with limited anticancer activity in advanced HCC.
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Registered trials
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