Spanish Oncology GenitoUrinary Group
1st Ibero-American Forum on
Metastatic Renal Cell Carcinoma:
Establishing A Continuum of Care
to Improve Patient Outcomes
14-15 March 2013. Buenos Aires,Argentina
Daniel Castellano
Oncología Médica.Unidad de Tumores GenitoUrinarios
Hospital Universitario 12 de Octubre.
I + 12 Research Institute.
Chairman SOGUG
Treatment options for metastatic RCC have been
revolutionised in a short period of time…
Pazopanib
(Oct 2009)6
Sunitinib
(Jan 2006)2
Sorafenib
(Dec 2005)1
High dose interleukin-2
Temsirolimus
(May 2007)3
IFN-α
1992-2005
1.
2.
3.
4.
5.
6.
7.
2005
US FDA. Sorafenib, 2005.
US FDA. Sunitinib malate, 2006.
US FDA. Temsirolimus, 2007.
US FDA. Everolimus, 2009.
US FDA. Bevacizumab, 2009.
US FDA. Pazopanib, 2009.
US FDA. Axitinib, 2012.
Bevacizumab + IFN-α
(Jul 2009)5
2006
2007
Axitinib
(Jan 2012)7
Everolimus
(Mar 2009)4
2008
2009
2010
2011
2012
Tivozanib
(2013 ??)
Algoritmo CCRm - 2013
Setting
Patients
Therapy
Options
First-line
Favourable- or
intermediate-risk
Sunitinib
Pazopanib
Tivozanib ?
Beva - IFN-α
HD IL-2
Cytokines
Sorafenib
Poor-risk
Temsirolimus
Sunitinib
Prior cytokine
Axitinib
Pazopanib
Sorafenib
Sunitinib
Prior VEGF–TKI
Axitinib
Sorafenib ?
Prior VEGF–TKI
Everolimus
Clinical trial
Prior TKI – TKI
Everolimus
Clinical Trial
Prior TKI – mTOR
Sorafenib/Dovitinib
Clinical trial
Second-line
Third-line
Adapted from EAU guidelines 2010,
ESMO Clinical Recommendations 2012,
NCCN guidelines 2013
SOGUG 2010
New pathways and therapies in RCC
More potent VEGFR2 TKIs
 Axitinib (confirmed)
 Tivozanib (confirmed)
Novel antiangiogenics





Angiopoietin inhibitor (not confirmed)
VEGFR2 antibody (pending)
DLL4 inhibitor (pending)
FGF Inhibitors (pending)
PI3K/Akt/mTOR inhibitors (early)
Novel immunotherapy
 Ipilimumab (stopped)
 Anti-PD-1 (pending)
 Anti-PDL-1 (stopped)
RCC = renal cell carcinoma; VEGFR = vascular endothelial growth factor receptor;
TKIs = tyrosine kinase inhibitors; DLL4 = delta-like-4.
Pal et al, 2010; Loges et al, 2010; Duignan et al, 2011.
Future Treatment options for metastatic RCC …
Anti-PD1
Sunitinib
(Adjuvant
Treatment)
Dovitinib
2013
2014
2015
Algoritmo CCRm – 2014?
Setting
Patients
Therapy
Options
First-line
Favourable- or
intermediate-risk
Sunitinib
Pazopanib
Tivozanib ?
Beva - IFN-α
HD IL-2
Cytokines
Sorafenib
Poor-risk
Temsirolimus
Sunitinib
Prior cytokine
Axitinib
Pazopanib
Sorafenib
Sunitinib
Prior VEGF–TKI
Axitinib
Sorafenib ?
Prior VEGF–TKI
Everolimus
Clinical trial
Prior TKI – TKI
Everolimus
Anti-PD1??
Clinical Trial
Prior TKI – mTOR
Sorafenib/Dovitinib
Clinical trial
Second-line
Third-line
Adapted from EAU guidelines 2010,
ESMO Clinical Recommendations 2012,
NCCN guidelines 2013
SOGUG 2010
Possible areas of unmet medical need
Currently approved treatments are not curative, and
Patients develop progressive disease
– Evolving need for effective therapeutics with unique
mechanisms of action for patients who progress
Non–clear cell histologies
– Few studies are available to determine efficacy
Biomarkers, new pathways,
gene profile,
mechanisms of resistance !!!
18
Manejo Integral Multidisciplinar del
Carcinoma Renal Avanzado
Tipo Tratamiento:
- Secuencial
- Individualización
Medicina Basada
Evidencia
(Est.Clínicos)
Manejo
Efectos
Adversos
Uso Racional de
Recursos
Tratamiento
Integral
Beneficio
Clínico
Control
Complicaciones
Tumorales
Spanish Oncology GenitoUrinary Group
2st Ibero-American Forum
on Metastatic Renal Cell
Carcinoma: Establishing A
Continuum of Care to
Improve Patient Outcomes
March 2014 ??
Muchas Gracias