A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma

2013 ◽  
Vol 39 (4) ◽  
pp. 388-401 ◽  
Author(s):  
Ahmed Alasker ◽  
Malek Meskawi ◽  
Maxine Sun ◽  
Salima Ismail ◽  
Nawar Hanna ◽  
...  
2011 ◽  
Vol 6 (3) ◽  
pp. 189-198 ◽  
Author(s):  
Marc R. Matrana ◽  
Bradley Atkinson ◽  
Eric Jonasch ◽  
Nizar M. Tannir

Author(s):  
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. The U.S. Food and Drug Administration (FDA) has thus approved a total of nine targeted therapies since 2005, including VEGF tyrosine kinase inhibitors (sunitinib, pazopanib, axitinib, sorafenib, and lenvatinib), a monoclonal antibody targeting VEGF (bevacizumab), mTOR inhibitors (temsirolimus and everolimus), and a multityrosine kinase inhibitor (cabozantinib). Furthermore, the development of immune checkpoint inhibitors has again shifted the mRCC therapeutic landscape with the FDA’s approval of nivolumab. Herein, we discuss the unprecedented changes in the field of clear cell histology mRCC in both the first-line and salvage settings, and we also discuss future therapies and recommend a treatment paradigm on sequencing of these agents.


2019 ◽  
Vol 17 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Nils Kroeger ◽  
Haoran Li ◽  
Guillermo De Velasco ◽  
Frede Donskov ◽  
Hao-Wen Sim ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15504-e15504
Author(s):  
James E. Signorovitch ◽  
Nicholas J. Vogelzang ◽  
Sumanta Kumar Pal ◽  
Peggy L. Lin ◽  
Daniel J. George ◽  
...  

e15504 Background: Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study aimed to compare practice-based effectiveness of these therapies in a recent chart review, and to compare findings with a previous chart review (Yang et al., 2012. ASCO). Methods: Community-based medical oncologists/hematologists (N=36) reviewed charts for ≤ 15 patients each. Included patients were aged ≥ 18 years, received a 1st-line TKI and initiated 2nd-line targeted therapy in 2010 or later. The primary outcome was time from 2nd-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving 2nd-line everolimus (EVE), temsirolimus (TEM), or TKI as a class (sunitinib, sorafenib, pazopanib or axitinib), using a multivariable Cox proportional hazards model adjusting for characteristics including type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled with previously-reported HRs for progression-free survival (PFS) from a previous chart review in a meta-analysis. Results: A total of 138, 64 and 79 patients received 2nd-line therapy with EVE, TEM or a TKI, respectively. Mean age was 63 years, mean duration of mRCC 13.5 months, and median follow-up 6 months. After adjusting for baseline characteristics, EVE was associated with a 28% and 26% reduction in the hazard of TTF compared to TEM and TKI, respectively. Pooling both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (Table). TTF differences between TEM and TKI were not significant. Conclusions: In two retrospective chart reviews EVE was associated with consistently reduced hazards of 2nd-line treatment failure in mRCC compared to TEM and TKIs. [Table: see text]


2014 ◽  
Vol 32 (3) ◽  
pp. 615-622 ◽  
Author(s):  
Laura-Maria Krabbe ◽  
Ahmed Q. Haddad ◽  
Mary E. Westerman ◽  
Vitaly Margulis

2012 ◽  
Vol 38 (2) ◽  
pp. 127-132 ◽  
Author(s):  
Bernard Escudier ◽  
Susanne Osanto ◽  
Börje Ljungberg ◽  
Camillo Porta ◽  
John Wagstaff ◽  
...  

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