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Cabozantinib and renal

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https://www.readbyqxmd.com/read/28105863/the-role-of-mtor-inhibition-as-second-line-therapy-in-metastatic-renal-carcinoma-clinical-evidence-and-current-challenges
#1
José Luis González-Larriba, Pablo Maroto, Ignacio Durán, Julio Lambea, Luis Flores, Daniel Castellano
Sequential treatment with targeted agents is the standard of care for patients with metastatic renal cell carcinoma (mRCC). Although first-line therapy with tyrosine kinase inhibitors (TKIs) is recommended for most patients, eventually all patients become resistant to them. Therefore, optimal selection of second-line therapy is crucial. Areas covered: We have reviewed the recent literature through pubmed search and recent congress presentations to briefly describe the clinical evidence for mTOR inhibition as a valid strategy in the treatment of mRCC after progression during anti-VEGFR therapy...
January 20, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28096936/treatment-options-in-advanced-renal-cell-carcinoma-after-first-line-treatment-with-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors
#2
REVIEW
Naveen S Basappa
Targeted therapy for metastatic renal cell carcinoma (mRCC) was introduced a decade ago and since then, a number of therapeutic options have been developed. Vascular endothelial growth factor-targeted therapy is the widely accepted first-line option for mRCC. After progression, treatment in the second-line setting has typically been with either axitinib or everolimus. However, with the advent of several new agents demonstrating efficacy in the second-line setting, including nivolumab, cabozantinib, and the combination of lenvatinib and everolimus, the treatment paradigm has shifted toward these novel therapies with improved patient outcomes...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28078236/cabozantinib-in-advanced-renal-cell-carcinoma-a-meteor-impact-on-clinical-practice
#3
EDITORIAL
Paolo Grassi, Elena Verzoni, Alessia Mennitto, Giuseppe Procopio
No abstract text is available yet for this article.
December 2016: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28062674/mixed-results-for-sunitinib-in-renal-cancer
#4
(no author information available yet)
Two studies presented at the European Society for Medical Oncology 2016 Congress evaluated sunitinib in patients with renal cell carcinomas. The first found that the drug prevents recurrence in patients who have had their cancerous kidney removed. The second study suggested that cabozantinib, approved for use as a second-line therapy, works better than sunitinib as a first-line treatment in patients with metastatic renal cell carcinoma.
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28035577/c-met-in-chromophobe-renal-cell-carcinoma
#5
Franziska Erlmeier, Philipp Ivanyi, Arndt Hartmann, Michael Autenrieth, Max Wiedemann, Wilko Weichert, Sandra Steffens
c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/27909994/cabozantinib-a-review-in-advanced-renal-cell-carcinoma
#6
Zaina T Al-Salama, Gillian M Keating
The multiple tyrosine kinase inhibitor (TKI) cabozantinib (Cabometyx™) is approved in the USA for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the EU, cabozantinib is indicated for the treatment of advanced RCC in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy. In adults with advanced or metastatic clear-cell RCC who had previously received VEGF receptor (VEGFR) TKIs, progression-free survival (PFS) and overall survival (OS) were significantly prolonged in patients who received oral cabozantinib versus oral everolimus in the pivotal METEOR trial...
December 2016: Drugs
https://www.readbyqxmd.com/read/27904650/cabozantinib-in-the-treatment-of-advanced-renal-cell-carcinoma-clinical-trial-evidence-and-experience
#7
REVIEW
Jose Manuel Ruiz-Morales, Daniel Y C Heng
The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI)...
December 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27890466/cabozantinib-improves-clinical-outcomes-in-renal-cancer
#8
Manjulika Das
No abstract text is available yet for this article.
January 2017: Lancet Oncology
https://www.readbyqxmd.com/read/27842445/cabozantinib-in-genitourinary-malignancies
#9
Tian Zhang, Se Eun Park, Cierra Hong, Daniel J George
Cabozantinib inhibits a variety of cellular receptors including VEGFR1-3, MET, AXL, RET, FLT3 and KIT. These signaling pathways have been shown to be important in genitourinary malignancies. Along its clinical development, it has shown most activity in advanced renal cell carcinoma; the METEOR study compared cabozantinib to everolimus and showed clinically and statistically significant improvements in both progression-free survival and overall survival. Herein, we review the development of cabozantinib in the genitourinary malignancies of renal cell carcinoma, prostate adenocarcinoma and urothelial carcinoma...
November 15, 2016: Future Oncology
https://www.readbyqxmd.com/read/27835047/cabozantinib-for-the-treatment-of-renal-cell-carcinoma
#10
Bernard Escudier, Julie C Lougheed, Laurence Albiges
Agents that target the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway as well as the PD-1 checkpoint inhibitor nivolumab are standard therapies for advanced renal cell carcinoma (RCC). Recently, cabozantinib, an inhibitor of MET, VEGF receptors, and AXL, was approved by the FDA and European Commission based on improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to standard of care treatment with everolimus in a randomized phase 3 trial in advanced RCC after prior VEGFR-tyrosine kinase inhibitor (TKI) therapy...
November 22, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27793960/u-s-food-and-drug-administration-approval-cabozantinib-for-treatment-of-advanced-renal-cell-carcinoma
#11
Harpreet Singh, Michael Brave, Julia A Beaver, Joyce Cheng, Shenghui Tang, Eias Zahalka, Todd R Palmby, Rajesh Venugopal, Pengfei Song, Qi Liu, Chao Liu, Jingyu Yu, Xiao Hong Chen, Xing Wang, Yaning Wang, Paul G Kluetz, Selena R Daniels, Elektra J Papadopoulos, Rajeshwari Sridhara, Amy E McKee, Amna Ibrahim, Geoffrey Kim, Richard Pazdur
On April 25, 2016, the U. S. Food and Drug Administration (FDA) approved cabozantinib (CABOMETYX{trade mark, serif}, Exelixis, Inc.) for the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy. The approval was based on data from one randomized, open-label, multicenter study in which RCC patients who had received prior anti-angiogenic therapy were treated with either cabozantinib 60 mg orally once daily (N=330) or everolimus 10 mg orally once daily (N=328)...
October 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27734291/clinical-pharmacokinetics-and-pharmacodynamics-of-cabozantinib
#12
Steven A Lacy, Dale R Miles, Linh T Nguyen
Cabozantinib inhibits receptor tyrosine kinases involved in tumor angiogenesis and metastasis. The capsule formulation (Cometriq(®)) is approved for the treatment of progressive metastatic medullary thyroid cancer at a 140-mg free base equivalent dose. The tablet formulation (Cabometyx™, 60-mg free base equivalent dose) is approved for the treatment of renal cell carcinoma following anti-angiogenic therapy. Cabozantinib displays a long terminal plasma half-life (~120 h) and accumulates ~fivefold by day 15 following daily dosing based on area under the plasma concentration-time curve (AUC)...
October 12, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27715452/cabozantinib-inhibits-tumor-growth-and-metastasis-of-a-patient-derived-xenograft-model-of-papillary-renal-cell-carcinoma-with-met-mutation
#13
Hongjuan Zhao, Rosalie Nolley, Andy M W Chan, Erinn B Rankin, Donna M Peehl
MET plays an important role in the development and progression of papillary renal cell carcinoma (pRCC). Evaluation of efficacy of MET inhibitors against pRCC has been hampered by limited preclinical models depicting MET abnormalities. We established a new patient-derived xenograft (PDX) model of pRCC carrying an activating mutation of MET and tested the ability of cabozantinib, an inhibitor of receptor tyrosine kinases including MET, to inhibit tumor growth and metastasis. Precision-cut, thin tissue slices from a pRCC specimen obtained by nephrectomy were implanted under the renal capsule of RAG2(-/-)γC(-/-) mice to establish first generation TSG-RCC-030...
August 11, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27713636/clinical-use-of-cabozantinib-in-the-treatment-of-advanced-kidney-cancer-efficacy-safety-and-patient-selection
#14
REVIEW
Steven S Yu, David I Quinn, Tanya B Dorff
Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib's designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27690664/emerging-growth-factor-receptor-antagonists-for-the-treatment-of-renal-cell-carcinoma
#15
Haris Zahoor, Brian I Rini
The landscape of systemic treatment for metastatic renal cell carcinoma (RCC) has dramatically changed with the introduction of targeted agents including vascular endothelial growth factor (VEGF) inhibitors. Recently, multiple new agents including growth factor receptor antagonists and a checkpoint inhibitor were approved for the treatment of refractory metastatic RCC based on encouraging benefit shown in clinical trials. Areas covered: The background and biological rationale of existing treatment options including a brief discussion of clinical trials which led to their approval, is presented...
December 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27664394/improvement-in-survival-end-points-of-patients-with-metastatic-renal-cell-carcinoma-through-sequential-targeted-therapy
#16
REVIEW
Emiliano Calvo, Manuela Schmidinger, Daniel Y C Heng, Viktor Grünwald, Bernard Escudier
Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti-VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab...
November 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27649009/cabozantinib-in-renal-cell-carcinoma-only-a-meteor-or-a-rising-star
#17
Melissa Bersanelli, Sebastiano Buti
N/A (Letter to the Editor).
2016: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/27630521/pharmaceutical-approval-update
#18
Mary Choy
Cabozantinib (Cabometyx) for advanced renal cell carcinoma; glycopyrrolate/formoterol fumarate (Bevespi Aerosphere) for chronic obstructive pulmonary disease; and ephedrine sulfate (Akovaz) for hypotension during anesthesia.
September 2016: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/27621699/everolimus-in-the-management-of-metastatic-renal-cell-carcinoma-an-evidence-based-review-of-its-place-in-therapy
#19
REVIEW
Sebastiano Buti, Alessandro Leonetti, Alice Dallatomasina, Melissa Bersanelli
INTRODUCTION: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, and its pathogenesis is strictly related to altered cellular response to hypoxia, in which mTOR signaling pathway is implicated. Everolimus, an mTOR serine/threonine kinase inhibitor, represents a therapeutic option for the treatment of advanced RCC. AIM: The objective of this article is to review the evidence for the treatment of metastatic RCC with everolimus. EVIDENCE REVIEW: Everolimus was approved for second- and third-line therapy in patients with advanced RCC according to the results of a Phase III pivotal trial that demonstrated a benefit in median progression-free survival of ~2 months compared to placebo after failure of previous lines of therapy, of which at least one was an anti-VEGFR tyrosine kinase inhibitor (TKI)...
2016: Core Evidence
https://www.readbyqxmd.com/read/27613167/the-wide-experience-of-the-sequential-therapy-for-patients-with-metastatic-renal-cell-carcinoma
#20
REVIEW
Julio Lambea, Urbano Anido, Olatz Etxániz, Luis Flores, Álvaro Montesa, Juan Manuel Sepúlveda, Emilio Esteban
Sequential targeted therapies are the standard of care for patients with metastatic renal cell carcinoma (mRCC). Several drugs are available for patients whose disease progresses while they receive initial tyrosine kinase inhibitor (TKI) therapy; these include nivolumab (an inhibitor of PD-1 receptor), everolimus (an inhibitor of the mechanistic target of rapamycin) or additional TKIs. Until now, there has been no clinical evidence to support the use of one strategy versus another, so investigators and physicians rely on experience, judgement and findings from molecular analyses to select the appropriate treatment...
November 2016: Current Oncology Reports
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