scholarly journals Pazopanib for the Treatment of Patients with Advanced Renal Cell Carcinoma

2010 ◽  
Vol 4 ◽  
pp. CMO.S4088 ◽  
Author(s):  
Joshua M. Lang ◽  
Michael R. Harrison
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tyrosine Kinases ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Pharmacokinetic Profile ◽  
Phase Iii ◽  
Advanced Renal Cell Carcinoma ◽  
National Meeting ◽  
Level I

Dramatic advances in the care of patients with advanced renal cell carcinoma have occurred over the last ten years, including insights into the molecular pathogenesis of this disease, that have now been translated into paradigm-changing therapeutic strategies. Elucidating the importance of signaling cascades related to angiogenesis is notable among these achievements. Pazopanib is a novel small molecule tyrosine kinase inhibitor that targets VEGFR-1, -2, and -3; PDGFR-α, PDGFR-β; and c-kit tyrosine kinases. This agent exhibits a distinct pharmacokinetic profile as well as toxicity profile compared to other agents in the class of VEGF signaling pathway inhibitors. This review will discuss the scientific rationale for the development of pazopanib, as well as preclinical and clinical trials that led to approval of pazopanib for patients with advanced renal cell carcinoma. The most recent information, including data from 2010 national meeting of the American Society of Clinical Oncology, and the design of ongoing Phase III trials, will be discussed. Finally, an algorithm utilizing Level I evidence for the treatment of patients with this disease will be proposed.

scholarly journals In silico modeling of combination systemic therapy for advanced renal cell carcinoma

2021 ◽  
Vol 9 (12) ◽  
pp. e004059
Author(s):  
Ritesh R Kotecha ◽  
Dennis J Hsu ◽  
Chung-Han Lee ◽  
Sujata Patil ◽  
Martin H Voss
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
In Silico ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Phase Iii ◽  
Advanced Renal Cell Carcinoma

Therapeutic combinations of VEGFR tyrosine kinase inhibitor plus immune checkpoint blockade now represent a standard in the first-line management of patients with advanced renal cell carcinoma. Tumor molecular profiling has shown notable heterogeneity when it comes to activation states of relevant pathways, and it is not clear that concurrent pursuit of two mechanisms of action is needed in all patients. Here, we applied an in silico drug model to simulate combination therapy by integrating previously reported findings from individual monotherapy studies. Clinical data was collected from prospective clinical trials of axitinib, cabozantinib, pembrolizumab and nivolumab. Efficacy of two-drug combination regimens (cabozantinib plus nivolumab, and axitinib plus pembrolizumab) was then modeled assuming independent effects of each partner. Reduction in target lesions, objective response rates (ORR), and progression-free survival (PFS) were projected based on previously reported activity of each agent, randomly pairing efficacy data from two source trials for individual patients and including only the superior effect of each pair in the model. In silico results were then contextualized to register phase III studies of these combinations with similar ORR, PFS, and best tumor response. As increasingly complex therapeutic strategies emerge, computational tools like this could help define benchmarks for trial designs and precision medicine efforts. Summary statement: In silico drug modeling provides meaningful insights into the effects of combination immunotherapy for patients with advanced kidney cancer.

Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial

The Lancet ◽  
2008 ◽  
Vol 372 (9637) ◽  
pp. 449-456 ◽  
Author(s):  
Robert J Motzer ◽  
Bernard Escudier ◽  
Stéphane Oudard ◽  
Thomas E Hutson ◽  
Camillo Porta ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Phase Iii ◽  
Advanced Renal Cell Carcinoma ◽  
Double Blind ◽  
Phase Iii Trial

scholarly journals Cabozantinib for the Management of Metastatic Clear Cell Renal Cell Carcinoma

2018 ◽  
Vol 5 (4) ◽  
pp. 1-5 ◽  
Author(s):  
Sharon Del Vecchio ◽  
Robert J Ellis
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Current Treatment ◽  
Phase Iii ◽  
Solid Organ ◽  
Cell Renal Cell Carcinoma ◽  
Randomised Controlled

Cabozantinib is a multi-tyrosine kinase inhibitor used for the treatment of various solid-organ tumours. It was recently approved as a first- and second-line therapeutic for the management of advanced/metastatic renal cell carcinoma based on the results of two randomised controlled trials. The phase III METEOR trial compared cabozantinib against everolimus as a second- or greater line therapy and found benefits in progression-free and overall survival, and the phase II CABOSUN trial compared cabozantinib against sunitinib as a first-line therapeutic and found benefits in terms of progression-free survival. This review briefly summarises how cabozantinib fits into current treatment paradigms for the management of advanced renal cell carcinoma.

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