ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
A Phase I Trial of the VEGF Receptor Tyrosine Kinase Inhibitor Pazopanib in Combination with the MEK Inhibitor Trametinib in Advanced Solid Tumors and Differentiated Thyroid Cancers.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- A Phase I Study of Dinaciclib in Combination With MK-2206 in Patients With Advanced Pancreatic Cancer.Clinical and translational science · 2020Trial
- Systemic Therapeutic Options in Radioiodine-Refractory Differentiated Thyroid Cancer: Current Indications and Optimal Timing.Cancers · 2025Review
- Efficacy and Safety of Pazopanib in the Treatment of Thyroid Cancer: A Systematic Review.Biomedicines · 2024Review
- Combining Multikinase Tyrosine Kinase Inhibitors Targeting the Vascular Endothelial Growth Factor and Cluster of Differentiation 47 Signaling Pathways Is Predicted to Increase the Efficacy of Antiangiogenic Combination Therapies.ACS pharmacology & translational science · 2023Article
- Response to BRAF-targeted Therapy Is Enhanced by Cotargeting VEGFRs or WNT/β-Catenin Signaling in BRAF-mutant Colorectal Cancer Models.Molecular cancer therapeutics · 2022Article
- PTEN regulates invasiveness in pancreatic neuroendocrine tumors through DUSP19-mediated VEGFR3 dephosphorylation.Journal of biomedical science · 2022Article
- Recent progress on vascular endothelial growth factor receptor inhibitors with dual targeting capabilities for tumor therapy.Journal of hematology & oncology · 2022Review
- Review
- Emerging strategies to target RAS signaling in human cancer therapy.Journal of hematology & oncology · 2021Review
- Novel Therapeutics in Radioactive Iodine-Resistant Thyroid Cancer.Frontiers in endocrinology · 2021Review
- Current Perspectives and Novel Strategies ofOncoTargets and therapy · 2021Review
- Pazopanib and Trametinib as a Synergistic Strategy against Osteosarcoma: Preclinical Activity and Molecular Insights.Cancers · 2020Article
- New Therapies for Advanced Thyroid Cancer.Frontiers in endocrinology · 2020Review
- An analysis of genetic heterogeneity in untreated cancers.Nature reviews. Cancer · 2019Review
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
purposeDifferentiated thyroid cancer (DTC) responds to VEGF receptor inhibitors. VEGF signals through RAS/RAF/MEK signaling. We evaluated the safety and efficacy of the VEGF receptor inhibitor pazopanib and MEK inhibitor trametinib in advanced solid tumors and DTC. PATIENTS AND
methodsPatients with advanced solid tumors were enrolled in a phase I, multicenter trial with a DTC expansion cohort. Patients received pazopanib 400-800 mg and trametinib 1-2 mg daily. Efficacy in the expansion cohort was assessed with objective response (OR) at 6 months of treatment.
resultsTwenty-six patients were enrolled in five dose levels. MTD was not reached; the recommended phase II dose was pazopanib 800 mg orally and trametinib 2 mg orally every day. There was one dose-limiting toxicity on dose level 1 with grade 3 fatigue and muscle weakness. Common grade 3 adverse events were elevated transaminases (19%), diarrhea (15%), hypertension (12%), and fatigue (8%). Thirteen patients were enrolled in the DTC cohort; OR was 33% (95% confidence interval, 9.9, 65.1%) and median progression-free survival was 10.7 months. The cohort was terminated after planned interim analysis suggested insufficiently increased activity against the historical control of pazopanib alone. Reduction in tumor diameter negatively correlated with p-ERK change in tumor (Spearman ρ = -0.71;
conclusionsPazopanib + trametinib was tolerable at full single-agent doses with clinical activity in DTC but did not achieve the prespecified response rate target.
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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.