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Cabozantinib and renal

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https://www.readbyqxmd.com/read/29283440/cabozantinib-a-multi-targeted-oral-tyrosine-kinase-inhibitor
#1
Jordan N Markowitz, Karen M Fancher
Cabozantinib is an oral, small-molecule, multitargeted tyrosine kinase inhibitor (TKI) that may confer an advantage over other TKIs that target a single receptor. It has been approved by the United States Food and Drug Administration for the treatment of both advanced renal cell carcinoma and progressive metastatic medullary thyroid cancer, and is being investigated for a wide array of other malignancies. Rationale for use, clinical trial data, and current recommendations for cabozantinib in renal cell cancer, thyroid cancer, prostate cancer, hepatocellular cancer, and lung cancer are detailed in this article...
December 28, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29223605/updated-european-association-of-urology-guidelines-recommendations-for-the-treatment-of-first-line-metastatic-clear-cell-renal-cancer
#2
REVIEW
Thomas Powles, Laurence Albiges, Michael Staehler, Karim Bensalah, Saeed Dabestani, Rachel H Giles, Fabian Hofmann, Milan Hora, Markus A Kuczyk, Thomas B Lam, Lorenzo Marconi, Axel S Merseburger, Sergio Fernández-Pello, Rana Tahbaz, Alessandro Volpe, Börje Ljungberg, Axel Bex
The randomised phase III clinical trial Checkmate-214 showed a survival superiority for the combination of ipilimumab and nivolumab when compared with the previous standard of care in first-line metastatic/advanced clear cell renal cell carcinoma (RCC) (Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: efficacy and safety of nivolumab plus ipilimumab vs sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups. LBA5, ESMO 2017, 2017)...
December 6, 2017: European Urology
https://www.readbyqxmd.com/read/29198329/examining-the-bleeding-incidences-associated-with-targeted-therapies-used-in-metastatic-renal-cell-carcinoma
#3
REVIEW
MacKenzie Crist, Elizabeth Hansen, Lipika Chablani, Elizabeth Guancial
A systematic review was conducted to illustrate the bleeding risks associated with targeted therapies used in the treatment of metastatic renal cell carcinoma (mRCC). Eligible studies included phase II, III, or IV clinical trials using pazopanib, sunitinib, cabozantinib, lenvatinib, everolimus, temsirolimus, bevacizumab, axitinib, and/or sorafenib in the setting of mRCC. Types of bleeding event(s), bleeding event frequency, and incidence of thrombocytopenia were collected from the relevant articles. ClinicalTrials...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29146618/management-of-adverse-events-associated-with-cabozantinib-therapy-in-renal-cell-carcinoma
#4
REVIEW
Manuela Schmidinger, Romano Danesi
Cabozantinib was recently approved for the treatment of advanced renal cell carcinoma (RCC) after treatment with vascular endothelial growth factor (VEGF)-targeted therapy. Cabozantinib is a multikinase inhibitor targeting VEGF receptor (VEGFR) 2, mesenchymal-epithelial transition receptor, and "anexelekto" receptor tyrosine kinase. A 60-mg daily dose led to improved overall survival and progression-free survival (PFS) versus everolimus in advanced RCC patients as a second- or later-line treatment in the METEOR trial...
November 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29134564/seom-clinical-guideline-for-treatment-of-kidney-cancer-2017
#5
E Gallardo, M J Méndez-Vidal, J L Pérez-Gracia, J M Sepúlveda-Sánchez, M Campayo, I Chirivella-González, X García-Del-Muro, A González-Del-Alba, E Grande, C Suárez
The goal of this article is to provide recommendations about the management of kidney cancer. Based on pathologic and molecular features, several kidney cancer variants were described. Nephron-sparing techniques are the gold standard of localized disease. After a randomized trial, sunitinib could be considered in adjuvant treatment in high-risk patients. Patients with advanced disease constitute a heterogeneous population. Prognostic classification should be considered. Both sunitinib and pazopanib are the standard options for first-line systemic therapy in advanced renal cell carcinoma...
November 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29089775/practical-management-of-adverse-events-associated-with-cabozantinib-treatment-in-patients-with-renal-cell-carcinoma
#6
REVIEW
Benjamin S Gerendash, Patricia A Creel
Cabozantinib is an oral tyrosine-kinase inhibitor whose targets include VEGFR, MET, and AXL. Cabozantinib is approved for the treatment of patients with advanced clear-cell renal-cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the pivotal Phase III trial of second-line RCC, cabozantinib was associated with a significant improvement in overall survival, progression-free survival, and antitumor response compared with everolimus. Adverse events (AEs) were common for patients receiving cabozantinib, but were effectively managed with supportive care and dose modifications, as discontinuations of cabozantinib due to an AE were infrequent...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29074560/a-network-meta-analysis-of-short-term-efficacy-of-different-single-drug-targeted-therapies-in-the-treatment-of-renal-cell-carcinoma
#7
Hong-Ling He, Wan-Xia Yao
The network meta-analysis was conducted to compare the short-term efficacy of different single-drug targeted therapies in the treatment of renal cell carcinoma (RCC). We initially searched databases for randomized controlled trials (RCTs) on different single-drug targeted therapies in treating RCC. The meta-analysis combined the direct and indirect evidence to calculate the pooled odds ratios (OR) and draw surface under the cumulative ranking curves (SUCRA). A total of 14 eligible RCTs were ultimately selected...
October 26, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29045250/clinical-decision-making-for-immunotherapy-in-metastatic-renal-cell-carcinoma
#8
Manuela Schmidinger
PURPOSE OF REVIEW: To review the treatment options in metastatic renal cell carcinoma (mRCC) in the light of new immunotherapy results. RECENT FINDINGS: Second-line treatment strategies for treatment of mRCC after progression on first-line VEGF-targeted therapy have recently undergone a major change. Treatment guidelines currently recommend the use of either nivolumab, a programmed cell death 1 (PD-1) inhibitor, or cabozantinib, an inhibitor of multiple receptor tyrosine kinases, as preferred choices...
October 17, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/29033542/axitinib-in-the-treatment-of-renal-cell-carcinoma-design-development-and-place-in-therapy
#9
REVIEW
Audrey Bellesoeur, Edith Carton, Jerome Alexandre, Francois Goldwasser, Olivier Huillard
Since 2005, the approved first-line treatment of metastatic renal cell carcinoma consists in tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptors (VEGFRs). Axitinib is an oral second-generation TKI and a potent VEGFR inhibitor with a half maximal inhibitory concentration for the VEGF family receptors 10-fold lower than other TKIs. Axitinib activity in renal cell carcinoma (RCC) patients has been studied in various settings and particularly as second-line treatment. In this setting, axitinib with clinically based dose escalation compared to sorafenib has demonstrated an improvement in progression-free survival in a randomized Phase III trial leading to US Food and Drug Administration approval...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28974985/cabozantinib-in-metastatic-renal-cell-carcinoma-latest-findings-and-clinical-potential
#10
REVIEW
Melissa Bersanelli, Sebastiano Buti
Since the advent of immunotherapy revolutionized the treatment of metastatic renal cell carcinoma (mRCC), the attention of oncologists has been unavoidably shifted from tyrosine kinase inhibitors (TKIs) to immune checkpoint blockade, with the associated risk of listing cabozantinib as just one of many available TKIs. On the contrary, we think that cabozantinib represents a very good option for mRCC treatment, with outstanding outcomes in terms of response rate, progression-free survival, overall survival and quick time to treatment response...
October 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28952411/clinical-development-of-mtor-inhibitors-for-renal-cancer
#11
REVIEW
Michele Ghidini, Fausto Petrelli, Antonio Ghidini, Gianluca Tomasello, Jens Claus Hahne, Rodolfo Passalacqua, Sandro Barni
Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. In the last 10 years, clinical trials have established multitargeted tyrosine kinase inhibitors (TKIs) as the standard first-line treatment in patients with metastatic disease. Multiple agents are now available for treatment in subsequent lines.The mammalian target of rapamycin (mTOR) inhibitors (e.g., everolimus alone or with lenvatinib) are among the most effective options. Areas covered: This paper provides a complete and updated overview on mTOR inhibitors for the treatment of advanced RCC...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28921623/one-step-synthesis-of-18-f-cabozantinib-for-use-in-positron-emission-tomography-imaging-of-c-met
#12
Vegard Torp Lien, Jo Klaveness, Dag Erlend Olberg
Cabozantinib is an FDA approved kinase inhibitor for the treatment of medullary thyroid cancer and advanced renal cell carcinoma, which exerts its therapeutic effect by inhibiting, among others, the tyrosine kinase c-Met. Non-invasive imaging techniques are becoming increasingly important clinically to ensure drug efficacy, staging, monitoring and patient stratification. PET isotope labelled tyrosine kinase inhibitors have, for the same reason, potential as PET tracers for imaging of various cancers. Based on cabozantinib, we synthesized the novel boronic acid pinacol ester 4 as a labelling precursor, where the boronic ester moiety replaces the fluorine native to this kinase inhibitor...
September 18, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28920492/recommendations-on-managing-lenvatinib-and-everolimus-in-patients-with-advanced-or-metastatic-renal-cell-carcinoma
#13
E Grande, H Glen, J Aller, G Argenziano, M J Lamas, P Ruszniewski, J L Zamorano, K Edmonds, S Sarker, M Staehler, J Larkin
There are several second-line treatment options for patients with renal cell carcinoma after first-line failure of a tyrosine kinase inhibitor, especially with the recent approvals of cabozantinib, nivolumab, and the lenvatinib plus everolimus combination. A lack of reliable biomarkers and an overall lack of prospective head-to-head comparisons make it a challenge to choose a second-line treatment in the clinic. Areas covered: In this review/meta-opinion, we describe the safety profile of the lenvatinib plus everolimus combination in renal cell carcinoma...
September 18, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28887097/second-line-systemic-therapy-in-metastatic-renal-cell-carcinoma-a-review
#14
REVIEW
Rohit K Jain, Shipra Gandhi, Saby George
Treatment in metastatic renal-cell carcinoma (mRCC) has evolved tremendously in the last decade. The development of newer targeted agents, like vascular endothelial growth factor inhibitors and immunotherapy have changed the treatment paradigm in mRCC patients. Axitinib and everolimus have been used extensively in patients who progressed on prior antiangiogenic therapy. The newer agents including nivolumab, cabozantinib, and lenvatinib in combination with everolimus have all demonstrated overall survival benefit over everolimus...
November 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28886175/cabozantinib-versus-everolimus-nivolumab-axitinib-sorafenib-and-best-supportive-care-a-network-meta-analysis-of-progression-free-survival-and-overall-survival-in-second-line-treatment-of-advanced-renal-cell-carcinoma
#15
Billy Amzal, Shuai Fu, Jie Meng, Johanna Lister, Helene Karcher
BACKGROUND: Relative effect of therapies indicated for the treatment of advanced renal cell carcinoma (aRCC) after failure of first line treatment is currently not known. The objective of the present study is to evaluate progression-free survival (PFS) and overall survival (OS) of cabozantinib compared to everolimus, nivolumab, axitinib, sorafenib, and best supportive care (BSC) in aRCC patients who progressed after previous VEGFR tyrosine-kinase inhibitor (TKI) treatment. METHODOLOGY & FINDINGS: Systematic literature search identified 5 studies for inclusion in this analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28879504/-tki%C3%A2-2-0-changes-in-the-medical-treatment-of-renal-cell-carcinoma
#16
REVIEW
V Stühler, S Kruck, M Hegemann, M Notohamiprodjo, T Todenhöfer, N Kröger, A Stenzl, J Bedke
Only for renal cell carcinoma (RCC) in a local stage curative treatment option by surgical resection exists. For metastatic disease the 5‑year survival rate decreases radically. A factor that contributes to this is the low sensibility to radiation and chemotherapeutics. Since the approval of the tyrosine kinase inhibitors in 2006 effective drugs for the treatment of mRCC is available. The specific inhibition of the vascular-endothelial-growth (VEGF)-receptor and the "mammalian Target of Rapamycin" (mTOR) leads to a prolongation of the progression-free survival as well as the overall survival rate...
September 6, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28800862/nice-guidance-on-cabozantinib-for-previously-treated-advanced-renal-cell-carcinoma
#17
Ahmed Elsada, Amanda I Adler
No abstract text is available yet for this article.
September 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28748331/eligibility-for-phase-3-clinical-trials-of-systemic-therapy-in-real-world-patients-with-metastatic-renal-cell-cancer-managed-in-a-rural-region
#18
Carsten Nieder, Mohsan A Syed, Astrid Dalhaug, Adam Pawinski, Jan Norum
Previous research has identified disparities between urban and rural cancer care, including clinical trial access. Therefore, we addressed three different questions in patients with metastatic renal cell cancer managed according to national guidelines in a rural Norwegian standard practice setting. (1) How many patients would have been eligible for three recent landmark randomized clinical trials? (2) Is survival different between eligible and non-eligible patients receiving first-line systemic therapy? (3) Is survival different between eligible patients and published trial results? We performed a retrospective analysis of 101 consecutive patients (2006-2016)...
September 2017: Medical Oncology
https://www.readbyqxmd.com/read/28650002/cabozantinib-use-in-renal-cell-carcinoma
#19
REVIEW
A J Neuwelt, S Mathur, A T Johnson, E R Kessler, D W Bowles
In the last several years, many new drugs have been approved to treat metastatic renal cell carcinoma (RCC). Cabozantinib is a novel multikinase inhibitor with activity against vascular endothelial growth factor receptor (VEGFR), proto-oncogene tyrosine-protein kinase receptor Ret and other kinases that recently joined this impressive list of approved agents. Cabozantinib is an active agent in the preclinical and clinical setting, having recently demonstrated superiority over everolimus in a blinded, randomized phase III study of patients with progressive RCC after at least one prior line of antiangiogenic therapy...
May 2017: Drugs of Today
https://www.readbyqxmd.com/read/28633552/cabozantinib-for-the-treatment-of-kidney-cancer
#20
REVIEW
Ahmed Abdelaziz, Ulka Vaishampayan
Cabozantinib is a small molecule tyrosine kinase inhibitor that initially showed activity in medullary thyroid cancer and was recently approved by the Food and Drug Administration for the treatment of metastatic renal cell carcinoma after progression on first line therapy. Areas covered: In the METEOR trial, cabozantinib demonstrated significantly improved efficacy in all three endpoints; response rates, progression free survival and overall survival in a randomized trial with everolimus as an active comparator...
July 2017: Expert Review of Anticancer Therapy
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