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Cabozantinib and renal

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https://www.readbyqxmd.com/read/28650002/cabozantinib-use-in-renal-cell-carcinoma
#1
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
#2
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
https://www.readbyqxmd.com/read/28590313/current-management-of-metastatic-renal-cell-carcinoma-evolving-new-therapies
#3
Ravi Kumar, Anil Kapoor
PURPOSE OF REVIEW: Targeted therapies have recently replaced cytokine treatments as the gold standard for management of metastatic renal cell carcinoma (mRCC). Currently approved treatments include the tyrosine kinase inhibitors sunitinib, pazopanib, axitinib, sorafenib, cabozantinib and lenvatinib; the vascular endothelial growth factor (VEGF) inhibitor bevacizumab; the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus; and the immunologic nivolumab. The purpose of this review is to provide an updated analysis of the clinical data supporting the use of these agents in the first-line and second-line setting...
June 5, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28561652/evolving-treatment-paradigm-in-metastatic-renal-cell-carcinoma
#4
David M Gill, Neeraj Agarwal, Ulka Vaishampayan
The treatment paradigm for advanced and metastatic renal cell carcinoma (mRCC) has evolved rapidly since the arrival of targeted therapies and novel immunotherapies. mRCC was previously treated only with cytokines. However, discoveries of mutations affecting the von Hippel-Lindau tumor suppressor gene (leading to increased expression of VEGF and hypoxia inducible factor/HIF-1) and of deregulations in the phosphatidylinositol-3 kinase/AKT/mTOR pathway (resulting in tumor angiogenesis, cell proliferation, and tumor growth) have led to the development of numerous targeted therapies...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28550387/correlation-of-c-met-expression-with-pd-l1-expression-in-metastatic-clear-cell-renal-cell-carcinoma-treated-by-sunitinib-first-line-therapy
#5
Solène-Florence Kammerer-Jacquet, Sarah Medane, Karim Bensalah, Jean-Christophe Bernhard, Mokrane Yacoub, Frantz Dupuis, Alain Ravaud, Grégory Verhoest, Romain Mathieu, Benoit Peyronnet, Angélique Brunot, Brigitte Laguerre, Alexandra Lespagnol, Jean Mosser, Frédéric Dugay, Marc-Antoine Belaud-Rotureau, Nathalie Rioux-Leclercq
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is highly metastatic. Cabozantinib, an anti-angiogenic tyrosine kinase inhibitor that targets c-MET, provided interesting results in metastatic ccRCC treatment. OBJECTIVE: To understand better the role of c-MET in ccRCC, we assessed its status in a population of patients with metastatic ccRCC. PATIENTS AND METHODS: For this purpose, tumor samples were analyzed for c-MET expression by immunohistochemistry (IHC), for c-MET copy number alterations by fluorescence in situ hybridization (FISH), and for c-MET mutations by next generation sequencing (NGS) in a retrospective cohort of 90 primary ccRCC of patients with metastases treated by first-line sunitinib...
May 26, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28549228/is-cabozantinib-really-better-than-sunitinib-as-first-line-treatment-of-metastatic-renal-cell-carcinoma
#6
Sebastiano Buti, Melissa Bersanelli
No abstract text is available yet for this article.
June 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28515249/incorporating-new-systemic-therapies-in-kidney-cancer-treatment
#7
Eric Jonasch
In 2017, pazopanib and sunitinib remain the mainstays of frontline therapy for advanced renal cell carcinoma. Independent review of frontline cabozantinib therapy may alter standard of care for patients at intermediate and poor risk. Multiple agents show a survival advantage in the second-line setting, including nivolumab, cabozantinib, and combination lenvatinib and everolimus. Selection of subsequent therapy will depend on patient disease status, comorbidities, and resource availability.
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28439491/translating-new-data-to-the-daily-practice-in-second-line-treatment-of-renal-cell-carcinoma-the-role-of-tumor-growth-rate
#8
EDITORIAL
Enrique Grande, Olga Martínez-Sáez, Pablo Gajate-Borau, Teresa Alonso-Gordoa
The therapeutic options for patients with metastatic renal cell carcinoma (mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased in daily practice and now it is not uncommon to see patients surviving kidney cancer for more than four to five years. Once treatment fails with the first line targeted therapy, head to head comparisons have shown that cabozantinib, nivolumab and the combination of lenvatinib plus everolimus are more effective than everolimus alone and that axitinib is more active than sorafenib...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#9
REVIEW
Aránzazu González Del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28417541/clinical-efficacy-of-cabozantinib-in-two-pediatric-patients-with-recurrent-renal-cell-carcinoma
#10
Mary Frances Wedekind, Mark Ranalli, Nilay Shah
Advanced-stage renal cell carcinoma (RCC) carries a dismal prognosis for pediatric patients with few studied therapeutic options. Cabozantinib is a small molecule tyrosine kinase inhibitor against the oncoprotein MET. It is currently approved by the U.S. Food and Drug administration for second-line treatment of RCC in adults. There is no published data on its use in children with RCC. We report here two pediatric patients with recurrent metastatic RCC whose tumors expressed MET and were treated with cabozantinib...
April 18, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28413127/evolution-of-circulating-tumor-dna-profile-from-first-line-to-subsequent-therapy-in-metastatic-renal-cell-carcinoma
#11
Sumanta K Pal, Guru Sonpavde, Neeraj Agarwal, Nicholas J Vogelzang, Sandy Srinivas, Naomi B Haas, Sabina Signoretti, Bradley A McGregor, Jeremy Jones, Richard B Lanman, Kimberly C Banks, Toni K Choueiri
BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails mechanistically distinct agents across the first- and second-line setting. Activity of these agents may be predicated on selective pressure that modulates RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA profile in a large cohort of mRCC patients, and to assess changes across patients receiving first-line and later lines of therapy...
April 13, 2017: European Urology
https://www.readbyqxmd.com/read/28403496/-interdisciplinary-recommendations-for-the-treatment-of-metastatic-renal-cell-carcinoma
#12
Kurt Miller, Lothar Bergmann, Christian Doehn, Jürgen Gschwend, Ulrich Keilholz
Thanks to the use of targeted therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved significantly. A median overall survival of more than 2 years is a realistic claim. These improvements are also reflected in recent discussions about 3 and more lines of therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib and pazopanib are also approved for second-line therapy, which, for pazopanib, is confined to the use after cytokine failure...
February 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#13
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28303494/current-management-strategy-for-metastatic-renal-cell-carcinoma-and-future-directions
#14
REVIEW
Hussein Merza, Marijo Bilusic
PURPOSE OF REVIEW: Major strides have been made in the treatment of kidney cancer in the last several years with checkpoint immunotherapies and novel targeted agents. This manuscript will review current treatment strategies for metastatic renal cell carcinoma and will discuss future directions. RECENT FINDINGS: Most recently, several new drugs including nivolumab, cabozantinib, and a combination of lenvatinib and everolimus have demonstrated acceptable toxicity and significantly improved overall survival, but evidence-based guidelines for sequencing of the approved treatment options and treatment selection based on biomarkers are still missing...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28286925/cabozantinib-for-renal-cell-carcinoma-current-and-future-paradigms
#15
REVIEW
Ahmed Abdelaziz, Ulka Vaishampayan
Cabozantinib was approved by the FDA in April 2016 for the treatment of advanced renal cancer, pretreated with at least one prior antiangiogenic therapy. This is the first agent in the therapy of kidney cancer to show a statistically significant improvement in all three endpoints of clinical efficacy, response rate, progression free survival, and overall survival (OS), in a phase III randomized trial. The reporting of METEOR coincided with that of the Checkmate 025 study which randomized similarly eligible patients to receive nivolumab or everolimus 10 mg daily...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28276433/renal-cell-carcinoma
#16
REVIEW
James J Hsieh, Mark P Purdue, Sabina Signoretti, Charles Swanton, Laurence Albiges, Manuela Schmidinger, Daniel Y Heng, James Larkin, Vincenzo Ficarra
Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance...
March 9, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28252459/renal-cell-carcinoma-molecular-characterization-and-evolving-treatment-paradigms
#17
Mark W Ball, Eric A Singer, Ramaprasad Srinivasan
PURPOSE OF REVIEW: The treatment landscape of advanced renal cell carcinoma (RCC) continues to shift as both new targeted therapies and immunotherapies show efficacy in treating the disease. Contemporary insights into the molecular characterization of RCC are likely to fuel the development of additional therapies. This review summarizes recent advancements in the biologic characterization of RCC and discusses newly approved therapies and ongoing studies in the treatment of advanced RCC...
March 1, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28247252/cabozantinib-an-active-novel-multikinase-inhibitor-in-renal-cell-carcinoma
#18
REVIEW
Nizar M Tannir, Gisela Schwab, Viktor Grünwald
Clear cell renal cell carcinoma (RCC) is characterized by inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL loss drives tumor angiogenesis and accounts for the clinical activity of VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs), the first-line standard of care for advanced RCC. Within the last year, three new second-line treatments have received FDA approval for use after anti-angiogenic therapy: the immune checkpoint inhibitor nivolumab, the TKI cabozantinib, and the combination of the TKI lenvatinib and the mTOR inhibitor everolimus...
February 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28224821/lenvatinib-for-use-in-combination-with-everolimus-for-the-treatment-of-patients-with-advanced-renal-cell-carcinoma-following-one-prior-anti-angiogenic-therapy
#19
REVIEW
Aine O'Reilly, James Larkin
In patients with mRCC options for second line therapies, following progression on anti-angiogenic agents, that demonstrate a survival advantage in clinical trials have been limited. Recently a number of agents have demonstrated efficacy in this setting. Here in we profile one such therapy, the combination of lenvatinib and everolimus, and discuss the expanded options for therapy available in this setting. Areas covered: In this review, we discuss current algorithms for treatment of mRCC in both the first-line and second-line setting...
March 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28223547/cabozantinib-targets-bone-microenvironment-modulating-human-osteoclast-and-osteoblast-functions
#20
Marco Fioramonti, Daniele Santini, Michele Iuliani, Giulia Ribelli, Paolo Manca, Nicola Papapietro, Filippo Spiezia, Bruno Vincenzi, Vincenzo Denaro, Antonio Russo, Giuseppe Tonini, Francesco Pantano
Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients...
March 21, 2017: Oncotarget
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