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Cabozantinib

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https://www.readbyqxmd.com/read/28634649/assessment-of-cabozantinib-treatment-on-qt-interval-in-a-phase-3-study-in-medullary-thyroid-cancer-evaluation-of-indirect-qt-effects-mediated-through-treatment-induced-changes-in-serum-electrolytes
#1
Dale R Miles, Steven A Lacy, David R Wada, Steve Milwee, Yifah Yaron, Linh T Nguyen
PURPOSE: This study evaluated factors impacting QTc interval in a phase 3 trial of cabozantinib in progressive, metastatic, medullary thyroid cancer (MTC). METHODS: Electrocardiogram (12-lead ECG) measurements were obtained at screening, and at pre-dose, and 2, 4, and 6 h post-dose on Days 1 and 29 in a phase 3 study in patients with MTC treated with cabozantinib (140 mg/day). Central tendency analyses were conducted on baseline-corrected QTc values. Linear and nonlinear mixed-effects models were used to evaluate potential factors affecting the QTc interval, including serum electrolytes, patient demographics, and cabozantinib concentration...
June 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28633552/cabozantinib-for-the-treatment-of-kidney-cancer
#2
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...
June 21, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28602103/advances-in-small-molecule-therapy-for-treating-metastatic-thyroid-cancer
#3
Jolanta Krajewska, Tomasz Gawlik, Barbara Jarzab
Multi kinase inhibitors (MKIs) are new drugs, which show activity against receptors of different growth factors leading to the inhibition of tumor cells growth and proliferation. This review summarizes a 10-year experience with the use of MKIs in thyroid cancer (TC). It focuses not only on sorafenib, lenvatinib, vandetanib and cabozantinib, already approved in TC, but also presents an overview of the results of different trials with distinct MKIs so far carried out in TC. Areas covered: published results of phase I, II and III studies and other reports evaluated the efficacy of different targeted drugs in TC...
June 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28599410/resistance-to-nanoparticle-albumin-bound-paclitaxel-is-mediated-by-abcb1-in-urothelial-cancer-cells
#4
Stefan Vallo, Raoul Köpp, Martin Michaelis, Florian Rothweiler, Georg Bartsch, Maximilian P Brandt, Kilian M Gust, Felix Wezel, Roman A Blaheta, Axel Haferkamp, Jindrich Cinatl
Nanoparticle albumin-bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro-apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5'-triphosphate-binding cassette transporter subfamily B, member 1 (ABCB1)...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28590313/current-management-of-metastatic-renal-cell-carcinoma-evolving-new-therapies
#5
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/28575860/in-vitro-and-in-vivo-anti-tumor-activity-of-alectinib-in-tumor-cells-with-ncoa4-ret
#6
Sachiko Arai, Kenji Kita, Azusa Tanimoto, Shinji Takeuchi, Koji Fukuda, Hiroshi Sato, Seiji Yano
Rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) accounts for approximately 1-2% of all NSCLCs. To date, RET fusions that involve at least six fusion partners in NSCLC, such as KIF5B, CCDC6, NCOA4, TRIM33, CLIP1, and ERC1, have been identified. Recent clinical trials for RET fusion-positive NSCLC using vandetanib or cabozantinib demonstrated positive clinical response and considerable differential activities for RET inhibitors among fusion partners. Alectinib, an approved ALK inhibitor, is reported to inhibit KIF5B-RET and CCDC6-RET...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28561652/evolving-treatment-paradigm-in-metastatic-renal-cell-carcinoma
#7
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
#8
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
#9
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
#10
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/28506408/genetics-of-medullary-thyroid-cancer-an-overview
#11
REVIEW
Giacomo Accardo, Giovanni Conzo, Daniela Esposito, Claudio Gambardella, Marco Mazzella, Filomena Castaldo, Carlo Di Donna, Andrea Polistena, Nicola Avenia, Vittorio Colantuoni, Dario Giugliano, Daniela Pasquali
Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved...
May 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28475408/vandetanib-and-cabozantinib-potentiate-mitochondria-targeted-agents-to-suppress-medullary-thyroid-carcinoma-cells
#12
Dmytro Starenki, Seung-Keun Hong, Pui-Kei Wu, Jong-In Park
Although the FDA-approved receptor tyrosine kinases inhibitors, vandetanib and cabozantinib, are used to treat surgically inoperable progressive medullary thyroid carcinoma (MTC), not all patients are responsive while the disease sometimes progresses after an initial response. To better understand MTC drug resistance at molecular and biochemical levels, we have generated drug-resistant subpopulations of the human MTC cell lines, TT and MZ-CRC-1, via prolonged exposure to vandetanib and cabozantinib. These drug-resistant progenies exhibited substantial cross-resistance to vandetanib and cabozantinib, suggesting that these inhibitors may invoke an overlapping resistance mechanism(s) in MTC cells...
May 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28465216/ros1-protein-tyrosine-kinase-inhibitors-in-the-treatment-of-ros1-fusion-protein-driven-non-small-cell-lung-cancers
#13
REVIEW
Robert Roskoski
ROS1 protein-tyrosine kinase fusion proteins are expressed in 1-2% of non-small cell lung cancers. The ROS1 fusion partners include CD74, CCDC6, EZR, FIG, KDELR2, LRIG3, MSN, SDC4, SLC34A2, TMEM106B, TMP3, and TPD52L1. Physiological ROS1 is closely related to the ALK, LTK, and insulin receptor protein-tyrosine kinases. ROS1 is a so-called orphan receptor because the identity of its activating ligand, if any, is unknown. The receptor is expressed during development, but little is expressed in adults and its physiological function is unknown...
April 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28447912/targeting-ret-in-patients-with-ret-rearranged-lung-cancers-results-from-the-global-multicenter-ret-registry
#14
Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A Janne, Mark M Awad, Nir Peled, Chul-Cho Byoung, Daniel D Karp, Michael Van Den Heuvel, Heather A Wakelee, Joel W Neal, Tony S K Mok, James C H Yang, Sai-Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R Gandara, Jonathan W Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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
#15
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
#16
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/28426123/cabozantinib-in-hepatocellular-carcinoma-results-of-a-phase-2-placebo-controlled-randomized-discontinuation-study
#17
R K Kelley, C Verslype, A L Cohn, T-S Yang, W-C Su, H Burris, F Braiteh, N Vogelzang, A Spira, P Foster, Y Lee, E Van Cutsem
Background: Cabozantinib, an orally bioavailable inhibitor of tyrosine kinases including MET, AXL, and VEGF receptors, was assessed in patients with hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation trial with nine tumor-type cohorts. Patients and methods: Eligible patients had Child-Pugh A liver function and ≤1 prior systemic anticancer regimen, completed ≥4 weeks before study entry. The cabozantinib starting dose was 100 mg daily...
March 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28417541/clinical-efficacy-of-cabozantinib-in-two-pediatric-patients-with-recurrent-renal-cell-carcinoma
#18
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
#19
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
#20
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
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