1. 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 Buenos Aires,Argentina
Daniel Castellano
Oncología Médica.Unidad de Tumores GenitoUrinarios
Hospital Universitario 12 de Octubre.
I + 12 Research Institute.
Chairman SOGUG

2. Bevacizumab + IFN-α (Jul 2009)5 High dose interleukin-2
Treatment options for metastatic RCC have been revolutionised in a short period of time…
Sunitinib (Jan 2006)2
Pazopanib (Oct 2009)6
Sorafenib (Dec 2005)1
Bevacizumab + IFN-α (Jul 2009)5
Axitinib (Jan 2012)7
High dose interleukin-2
Temsirolimus (May 2007)3
Everolimus (Mar 2009)4
IFN-α
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.
Tivozanib (2013 ??)

3. Algoritmo CCRm - 2013 Sunitinib Pazopanib Tivozanib ? Beva - IFN-α
Setting
Patients
Therapy
Options
First-line
Favourable- or
intermediate-risk
Sunitinib
Pazopanib
Tivozanib ?
Beva - IFN-α
HD IL-2
Cytokines Sorafenib
Poor-risk
Temsirolimus
Second-line
Prior cytokine
Axitinib
Sorafenib
Prior VEGF–TKI
Sorafenib ?
Everolimus
Clinical trial
Third-line
Prior TKI – TKI
Everolimus
Clinical Trial
Prior TKI – mTOR
Sorafenib/Dovitinib
Clinical trial
Adapted from EAU guidelines 2010,
ESMO Clinical Recommendations 2012,
NCCN guidelines 2013
SOGUG 2010 3

4. 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.

5. Sunitinib (Adjuvant Treatment)
Future Treatment options for metastatic RCC …
Anti-PD1
Sunitinib (Adjuvant Treatment)
Dovitinib

6. Algoritmo CCRm – 2014? Sunitinib Pazopanib Tivozanib ? Beva - IFN-α
Setting
Patients
Therapy
Options
First-line
Favourable- or
intermediate-risk
Sunitinib
Pazopanib
Tivozanib ?
Beva - IFN-α
HD IL-2
Cytokines Sorafenib
Poor-risk
Temsirolimus
Second-line
Prior cytokine
Axitinib
Sorafenib
Prior VEGF–TKI
Sorafenib ?
Everolimus
Clinical trial
Third-line
Prior TKI – TKI
Everolimus
Anti-PD1??
Clinical Trial
Prior TKI – mTOR
Sorafenib/Dovitinib
Clinical trial
Adapted from EAU guidelines 2010,
ESMO Clinical Recommendations 2012,
NCCN guidelines 2013
SOGUG 2010 6

7. 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

8. Manejo Integral Multidisciplinar del Carcinoma Renal Avanzado
Tipo Tratamiento:
Secuencial
Individualización
Medicina Basada Evidencia
(Est.Clínicos)
Uso Racional de Recursos
Tratamiento
Integral
Manejo
Efectos Adversos
Control Complicaciones Tumorales
Beneficio
Clínico 8

9. Spanish Oncology GenitoUrinary Group
2st Ibero-American Forum on Metastatic Renal Cell Carcinoma: Establishing A Continuum of Care to Improve Patient Outcomes March 2014 ??

10. Muchas Gracias