1st Ibero-American Forum on Metastatic Renal Cell

Carcinoma: Establishing A Continuum of Care to

Improve Patient Outcomes

Daniel CastellanoOncología Médica.Unidad de Tumores

GenitoUrinariosHospital Universitario 12 de Octubre.

I + 12 Research Institute. Chairman SOGUG

14-15 March 2013. Buenos Aires,Argentina

Spanish Oncology GenitoUrinary Group

1. US FDA. Sorafenib, 2005.2. US FDA. Sunitinib malate, 2006.3. US FDA. Temsirolimus, 2007.4. US FDA. Everolimus, 2009.5. US FDA. Bevacizumab, 2009.6. US FDA. Pazopanib, 2009.7. US FDA. Axitinib, 2012.

1992-2005 2005 2006 2007 2008 2009 2010 2011 2012 1992-2005 2005 2006 2007 2008 2009 2010 2011 2012

IFN-α

High dose interleukin-2

Sunitinib (Jan 2006)2

Sorafenib (Dec 2005)1

Temsirolimus (May 2007)3

Pazopanib (Oct 2009)6

Bevacizumab + IFN-α(Jul 2009)5

Everolimus (Mar 2009)4

Axitinib (Jan 2012)7

Treatment options for metastatic RCC have been revolutionised in a short period of time…

Tivozanib (2013 ??)

Algoritmo CCRm - 2013Setting Patients Therapy Options

First-line Favourable- or

intermediate-riskSunitinib

Pazopanib

Tivozanib ?

Beva - IFN-α

HD IL-2

CytokinesSorafenib

Poor-risk Temsirolimus Sunitinib

Second-line Prior cytokine Axitinib

Pazopanib

Sorafenib

Sunitinib

Prior VEGF–TKI Axitinib Sorafenib ?

Prior VEGF–TKI Everolimus Clinical trial

Adapted from EAU guidelines 2010, ESMO Clinical Recommendations 2012,

NCCN guidelines 2013SOGUG 2010

Third-line Prior TKI – TKI Everolimus Clinical Trial

Prior TKI – mTOR Sorafenib/Dovitinib Clinical trial

New pathways and therapies in RCCMore 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.

2013 2014 2015 2013 2014 2015

Dovitinib

Anti-PD1

Sunitinib (Adjuvant

Treatment)

Future Treatment options for metastatic RCC …

Algoritmo CCRm – 2014?Setting Patients Therapy Options

First-line Favourable- or

intermediate-riskSunitinib

Pazopanib

Tivozanib ?

Beva - IFN-α

HD IL-2

CytokinesSorafenib

Poor-risk Temsirolimus Sunitinib

Second-line Prior cytokine Axitinib

Pazopanib

Sorafenib

Sunitinib

Prior VEGF–TKI Axitinib Sorafenib ?

Prior VEGF–TKI Everolimus Clinical trial

Adapted from EAU guidelines 2010, ESMO Clinical Recommendations 2012,

NCCN guidelines 2013SOGUG 2010

Third-line Prior TKI – TKI Everolimus

Anti-PD1??

Clinical Trial

Prior TKI – mTOR Sorafenib/Dovitinib Clinical trial

18

Possible areas of unmet medical need

Currently approved treatments are not curative, and Patients develop progressive disease

– Evolving need for effective therapeutics with uniquemechanisms 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 !!!

Tipo Tipo Tratamiento:Tratamiento:

- Secuencial Secuencial - IndividualizaciIndividualizaci

ónón

Control Control ComplicacioneComplicaciones Tumoraless Tumorales

Tratamiento

IntegralManejo Manejo Efectos Efectos

AdversosAdversos

Medicina Basada

Evidencia(Est.Clínicos)

Uso Racional de Recursos

Beneficio Clínico

Manejo Integral Multidisciplinar del Carcinoma

Renal Avanzado

2st Ibero-American Forum on Metastatic Renal Cell Carcinoma:

Establishing A Continuum of Care to

Improve Patient Outcomes

March 2014 ??

Spanish Oncology GenitoUrinary Group

Muchas Gracias