Topic
Cabozantinib
About: Cabozantinib is a research topic. Over the lifetime, 1026 publications have been published within this topic receiving 25192 citations. The topic is also known as: BMS907351 & Cabometyx®.
Papers
More filters
21 Jan 2021
TL;DR: In this paper, the authors used non-invasive criteria to diagnose hepatocellular carcinoma (HCC) and showed that 25% of all HCCs present potentially actionable mutations, which are yet to translate into clinical practice.
Abstract: Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025 Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies The current major advancements have impacted the management of patients with advanced HCC Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages
2,038 citations
Memorial Sloan Kettering Cancer Center1, University College London2, National Taiwan University3, University of Southern California4, University of Ulsan5, Trakya University6, University of Bordeaux7, University of Bologna8, University of Amsterdam9, The Chinese University of Hong Kong10, University of California, San Francisco11
TL;DR: Treatment with cabozantinib resulted in longer overall survival and progression‐free survival than placebo among patients with previously treated advanced hepatocellular carcinoma, and the rate of high‐grade adverse events in the cabozaninib group was approximately twice that observed in the placebo group.
Abstract: Background Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellul...
1,471 citations
TL;DR: Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC, and met its primary objective of PFS prolongation with vandETanib versus placebo.
Abstract: Purpose There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC.
1,201 citations
TL;DR: Treatment with cabozantinib is suggested to be a promising agent for inhibiting tumor angiogenesis and metastasis in cancers with dysregulated MET and VEGFR signaling.
Abstract: The signaling pathway of the receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF) is important for cell growth, survival, and motility and is functionally linked to the signaling pathway of VEGF, which is widely recognized as a key effector in angiogenesis and cancer progression. Dysregulation of the MET/VEGF axis is found in a number of human malignancies and has been associated with tumorigenesis. Cabozantinib (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, KIT, AXL, and FLT3. Treatment with cabozantinib inhibited MET and VEGFR2 phosphorylation in vitro and in tumor models in vivo and led to significant reductions in cell invasion in vitro . In mouse models, cabozantinib dramatically altered tumor pathology, resulting in decreased tumor and endothelial cell proliferation coupled with increased apoptosis and dose-dependent inhibition of tumor growth in breast, lung, and glioma tumor models. Importantly, treatment with cabozantinib did not increase lung tumor burden in an experimental model of metastasis, which has been observed with inhibitors of VEGF signaling that do not target MET. Collectively, these data suggest that cabozantinib is a promising agent for inhibiting tumor angiogenesis and metastasis in cancers with dysregulated MET and VEGFR signaling. Mol Cancer Ther; 10(12); 2298–308. ©2011 AACR .
1,041 citations
Harvard University1, Institut Gustave Roussy2, Queen Mary University of London3, Cleveland Clinic4, Aarhus University5, Johns Hopkins University6, Baylor University7, University of Ulsan8, University of Helsinki9, Washington University in St. Louis10, University of Toronto11, Seoul National University12, Autonomous University of Barcelona13, Tom Baker Cancer Centre14, Medical University of Vienna15, Exelixis16, University of Texas MD Anderson Cancer Center17, Memorial Sloan Kettering Cancer Center18
TL;DR: Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.
Abstract: BackgroundCabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. MethodsWe randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression-free survival. Secondary efficacy end points were overall survival and objective response rate. ResultsMedian progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] ...
963 citations