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https://www.readbyqxmd.com/read/29784745/updates-to-the-management-of-kidney-cancer
#1
Eric Jonasch
Several updates were made to the 2018 NCCN Guidelines for Kidney Cancer. Adjuvant sunitinib is the first adjuvant therapy to be endorsed by the panel for patients with stage II and III clear cell histology renal cell carcinoma (RCC; category 2B). A promising new treatment-ipilimumab plus nivolumab for patients at intermediate and poor risk in the frontline setting-was added to the guidelines as well. Cabozantinib was added as a first-line option for poor- and intermediate-risk patients with advanced RCC.
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29783126/systemic-therapy-for-intermediate-and-advanced-hepatocellular-carcinoma-sorafenib-and-beyond
#2
REVIEW
Jean-Luc Raoul, Masatoshi Kudo, Richard S Finn, Julien Edeline, Maria Reig, Peter R Galle
The hepatocellular carcinoma (HCC) treatment landscape changed a decade ago, with sorafenib demonstrating survival benefit in the first-line setting and becoming the first systemic therapy to be approved for HCC. More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab). A key recommendation in the management of patients receiving sorafenib is to promote close communication between the patient and the physician so that adverse events (AEs) are detected early and severe AEs can be prevented...
May 17, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29769293/emerging-multitarget-tyrosine-kinase-inhibitors-in-the-treatment-of-neuroendocrine-neoplasms
#3
Federica Grillo, Tullio Florio, Francesco Ferraù, Elda Kara, Giuseppe Fanciulli, Antongiulio Faggiano, Annamaria A L Colao
In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multi-target tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by regulatory agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in depth review on the studies published on the following MTKIs in neuroendocrine tumours: axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performed...
May 16, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29753637/safety-and-efficacy-of-cabozantinib-in-metastatic-renal-cell-carcinoma-real-world-data-from-an-italian-managed-access-program
#4
Giuseppe Procopio, Michele Prisciandaro, Roberto Iacovelli, Enrico Cortesi, Giuseppe Fornarini, Gaetano Facchini, Giacomo Cartenì, Roberto Sabbatini, Gabriella Del Bene, Luca Galli, Claudia Caserta, Andrea Giovanni Multari, Marco Bregni, Francesco Massari, Sebastiano Buti, Ugo De Giorgi, Fable Zustovich, Michele Milella, Fabio Calabrò, Maria Laura Mancini, Giampaolo Tortora, Claudio Vernieri, Daniele Santini, Mariella Sorarù, Riccardo Ricotta, Cristina Masini, Marcello Tucci, Stefano Luzi Fedeli, Cinzia Ortega, Antonella Mecozzi, Raffaele Ratta, Cora N Sternberg, Elena Verzoni
BACKGROUND: The randomized phase 3 METEOR study confirmed a survival benefit of cabozantinib over everolimus in patients with metastatic renal-cell carcinoma (mRCC) with disease that progressed after treatment with at least one previous antiangiogenic inhibitor. The aim of this analysis was to evaluate the safety and activity of cabozantinib in an unselected population. METHODS: Data were collected across 24 Italian centers. Cabozantinib therapy was initiated at physician request between September and December 2016...
April 19, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29741507/cabozantinib-approved-for-first-line-treatment-of-advanced-renal-cell-carcinoma
#5
(no author information available yet)
No abstract text is available yet for this article.
February 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29739622/phase-ii-study-of-single-agent-cabozantinib-in-patients-with-recurrent-clear-cell-ovarian-primary-peritoneal-or-fallopian-tube-cancer-nrg-gy001
#6
Panagiotis A Konstantinopoulos, William E Brady, John Farley, Amy Armstrong, Denise S Uyar, David M Gershenson
OBJECTIVE: To evaluate the efficacy and tolerability of cabozantinib in recurrent clear cell ovarian, primary peritoneal or fallopian tube cancer. METHODS: Patients with recurrent ovarian, fallopian or primary peritoneal tumors with at least 50% clear cell histomorphology, measurable disease, one or two prior regimens and ECOG performance status 0-2 received cabozantinib 60 mg orally once daily continuously, in 4-week cycles until disease progression or unacceptable toxicity...
May 5, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29727493/erratum-fathi-at-blonquist-tm-hernandez-d-et-al-cabozantinib-is-well-tolerated-in-acute-myeloid-leukemia-and-effectively-inhibits-the-resistance-conferring-flt3-tyrosine-kinase-domain-f691-mutation-cancer-2018-124-306-314
#7
https://www.readbyqxmd.com/read/29719414/cost-effectiveness-comparison-of-cabozantinib-with-everolimus-axitinib-and-nivolumab-in-the-treatment-of-advanced-renal-cell-carcinoma-following-the-failure-of-prior-therapy-in-england
#8
Jie Meng, Johanna Lister, Anne-Lise Vataire, Roman Casciano, Jerome Dinet
Purpose: The aim of this study was to compare the cost-effectiveness of cabozantinib with the standard of care in England in adult patients with advanced renal cell carcinoma (aRCC), following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy. Methods: We developed a partitioned-survival model with three health states to assess the cost-effectiveness of cabozantinib and its comparators. The model time horizon was 30 years. Efficacy and safety data were derived from pivotal clinical trials (METEOR: NCT01865747, CheckMate025: NCT01668784, and AXIS: NCT00678392)...
2018: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/29708353/-treatment-of-metastatic-renal-cell-carcinoma
#9
Igor Richter, Josef Dvořák
INTRODUCTION: Renal cell cancer accounts for approximately 2-3% of all cases of malignancy. The incidence of kidney cancer in the Czech Republic is the highest in the world. Approximately 70% of renal cell carcinomas are clear-cell renal cancer. Various treatment options for metastatic renal cell cancer (mRCC) have been developed. Treatment regimens comprise antiangiogenic drugs in combination with vascular endothelial growth factor receptor inhibitors, mTOR inhibitors, and immunotherapy...
2018: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29706615/clinical-benefit-from-tyrosine-kinase-inhibitors-in-metastatic-merkel-cell-carcinoma-a-case-series-of-5-patients
#10
Erica S Tarabadkar, Hannah Thomas, Astrid Blom, Upendra Parvathaneni, Thomas Olencki, Paul Nghiem, Shailender Bhatia
BACKGROUND Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer. The estimated 5-year survival of patients with metastatic disease is approximately 14%. Cytotoxic chemotherapy is associated with a modest median progression-free survival (PFS) of only 3 months. In recent studies, immunotherapy with anti-PD-1/anti-PD-L1 antibodies has demonstrated a high response rate in immunocompetent patients (>50% in chemotherapy-naïve patients) and responses are typically durable. However, approximately 50% of immunocompetent patients do not respond to immunotherapy...
April 30, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/29704768/management-of-treatment-related-toxicities-in-advanced-medullary-thyroid-cancer
#11
REVIEW
Marcia S Brose, Keith C Bible, Laura Q M Chow, Jill Gilbert, Carolyn Grande, Francis Worden, Robert Haddad
Progress in the treatment of advanced medullary thyroid cancer (MTC) has resulted from the approval of 2 drugs within the past 5 years, vandetanib and cabozantinib. These multikinase inhibitors (MKIs) possess overlapping specificities for multiple kinase targets implicated in the progression of MTC. Both drugs are associated with toxicities, including hypertension, hemorrhage/perforation, diarrhea and other gastrointestinal events, several dermatologic events, and hypothyroidism. In addition, vandetanib is uniquely associated with QTc prolongation through interaction with myocardial potassium channels, and cabozantinib is uniquely associated with hand-foot skin reaction...
April 22, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29693796/a-phase-1-study-of-cabozantinib-in-children-and-adolescents-with-recurrent-or-refractory-solid-tumors-including-cns-tumors-trial-advl1211-a-report-from-the-children-s-oncology-group
#12
Meredith K Chuk, Brigitte C Widemann, Charles G Minard, Xiaowei Liu, AeRang Kim, Melanie Brooke Bernhardt, Rachel A Kudgus, Joel M Reid, Stephan D Voss, Susan Blaney, Elizabeth Fox, Brenda J Weigel
BACKGROUND: We conducted a phase 1 trial to determine the maximum tolerated dose (MTD), toxicity profile, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary activity of cabozantinib in children with refractory or relapsed solid tumors. METHODS: Patients received cabozantinib tablets on a continuous dosing schedule in a rolling-six escalating phase 1 trial design. PK and PD studies were performed. RESULTS: Forty-one patients, median (range) age 13 (4-18) years, received cabozantinib to achieve a weekly cumulative dose equivalent to 30 (n = 6), 40 (n = 23)...
April 25, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29688429/ef24-a-curcumin-analog-and-zstk474-emphasizes-the-effect-of-cabozantinib-in-medullary-thyroid-cancer
#13
Loris Bertazza, Francesca Sensi, Elisabetta Cavedon, Sara Watutantrige-Fernando, Simona Censi, Jacopo Manso, Federica Vianello, Eric Casal Ide, Maurizio Iacobone, Raffaele Pezzani, Caterina Mian, Susi Barollo
XL184 is a small-molecule kinase inhibitor recently included in first-line systemic therapy for patients with advanced, progressive medullary thyroid cancer (MTC). EF24 is a curcumin analog with a high bio-availability, and ZSTK474 is an inhibitor of the PI3K signaling pathway. We investigated the effect of these compounds, alone and in combination, in two RET-mutated TT and MZ-CRC-1 MTC cell lines, and in six mostly RET wild-type human MTC primary cultures. Low IC50 values demonstrated the efficacy of the drugs, while the Combination Index revealed a significant synergistic effect of combinations of XL184+ZSTK474 and XL184+EF24...
April 23, 2018: Endocrinology
https://www.readbyqxmd.com/read/29687244/a-population-pharmacokinetic-model-of-cabozantinib-in-healthy-volunteers-and-patients-with-various-cancer-types
#14
Steven Lacy, Bei Yang, Jace Nielsen, Dale Miles, Linh Nguyen, Matt Hutmacher
PURPOSE: An integrated population pharmacokinetic (popPK) model was developed to describe the pharmacokinetics (PK) of tyrosine kinase inhibitor cabozantinib in healthy volunteers (HVs) and patients with various cancer types and to identify any differences in cabozantinib PK across these populations. METHODS: Plasma concentration data used to develop the popPK model were obtained from nine clinical trials (8072 concentrations from 1534 HVs or patients) of cabozantinib in HVs and patients with renal cell carcinoma (RCC), medullary thyroid carcinoma (MTC), glioblastoma multiforme, castration-resistant prostate cancer, or other advanced malignancies...
April 23, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29667066/population-exposure-response-analysis-of-cabozantinib-efficacy-and-safety-endpoints-in-patients-with-renal-cell-carcinoma
#15
Steven Lacy, Jace Nielsen, Bei Yang, Dale Miles, Linh Nguyen, Matt Hutmacher
BACKGROUND: In the phase III METEOR trial, tyrosine kinase inhibitor cabozantinib significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival compared to everolimus in patients with advanced renal cell carcinoma (RCC) who had received prior VEGFR inhibitor therapy. In METEOR, RCC patients started at a daily 60-mg cabozantinib tablet (Cabometyx™) dose but could reduce to 40- or 20-mg to achieve a tolerated exposure. OBJECTIVES AND METHODS: Exposure-response (ER) models were developed to characterize the relationship between cabozantinib at clinically relevant exposures in RCC patients enrolled in METEOR and efficacy (PFS and tumor response) and safety endpoints...
April 17, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29662541/cabozantinib-in-the-treatment-of-advanced-renal-cell-carcinoma-in-adults-following-prior-vascular-endothelial-growth-factor-targeted-therapy-clinical-trial-evidence-and-experience
#16
REVIEW
Susanne Osanto, Tom van der Hulle
Cabozantinib is an oral multitargeted tyrosine kinase inhibitor (TKI) that potently inhibits MET and AXL, both associated with poor prognosis in renal cell carcinoma (RCC), next to vascular endothelial growth factor receptor 2, KIT, FLT3 and RET. Chronic treatment with vascular endothelial growth factor receptor (VEGFR)-targeting sunitinib upregulates MET and AXL in RCC, indicating that cabozantinib may be particularly effective in patients with advanced RCC whose disease progressed on prior VEGFR-targeted treatment...
March 2018: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/29660005/volumetric-response-quantified-using-t1-subtraction-predicts-long-term-survival-benefit-from-cabozantinib-monotherapy-in-recurrent-glioblastoma
#17
Benjamin M Ellingson, Dana T Aftab, Gisela M Schwab, Colin Hessel, Robert J Harris, Davis C Woodworth, Kevin Leu, Ararat Chakhoyan, Catalina Raymond, Jan Drappatz, John de Groot, Michael D Prados, David A Reardon, David Schiff, Marc Chamberlain, Tom Mikkelsen, Annick Desjardins, Jaymes Holland, Jerry Ping, Ron Weitzman, Patrick Y Wen, Timothy F Cloughesy
Background: To overcome challenges with traditional response assessment in anti-angiogenc agents, the current study uses T1 subtraction maps to quantify volumetric radiographic response in cabozantinib monotherapy, an orally bioavailable tyrosine kinase inhibitor with activity against VEGFR2, MET, and AXL, in an open-label, phase II trial in patients with recurrent glioblastoma (NCT00704288). Methods: A total of 108 patients with adequate imaging data and confirmed recurrent GBM were included in this retrospective study from a phase II multicenter trial of cabozantinib monotherapy (XL184-201) at either 100mg (N=87) or 140mg (N=21) per day...
April 5, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29656939/management-of-metastatic-collecting-duct-carcinoma-an-encouraging-result-in-a-patient-treated-with-cabozantinib
#18
Alessia Mennitto, Elena Verzoni, Giorgia Peverelli, Alessandra Alessi, Giuseppe Procopio
No abstract text is available yet for this article.
March 27, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29656851/first-line-systemic-therapy-for-metastatic-renal-cell-carcinoma-a-systematic-review-and-network-meta-analysis
#19
REVIEW
Christopher J D Wallis, Zachary Klaassen, Bimal Bhindi, Xiang Y Ye, Thenappan Chandrasekar, Ann M Farrell, Hanan Goldberg, Stephen A Boorjian, Bradley Leibovich, Girish S Kulkarni, Prakesh S Shah, Georg A Bjarnason, Daniel Heng, Raj Satkunasivam, Antonio Finelli
CONTEXT: In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents. OBJECTIVE: To indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC. EVIDENCE ACQUISITION: Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017...
April 13, 2018: European Urology
https://www.readbyqxmd.com/read/29587324/-immunotherapy-for-renal-cell-carcinoma-current-status
#20
Marc-Oliver Grimm, Susan Foller
Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially changed during the last 2 years due to approval of the immune-checkpoint inhibitor Nivolumab (Opdivo® ) and new multikinase inhibitors (Cabozantinib, Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted therapy. CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs...
April 2018: Aktuelle Urologie
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