¿Cómo Incorporar la Terapia Antiangiogénica en el Cáncer de Ovario?

XIV Congreso Nacional Salamanca Octubre de 2013 SESION CONTROVERSIA-1 15,45-17H

Andres Poveda Fundación Instituto Valenciano de Oncología

acog@fivo.org

Progress in the Management of Ovarian Cancer: Evolution Over 40 Years

Five-year

survival 15% 30% 40% 50%?

First

use

of

cisplatin

First

use

of

carboplatin

First

use

of

paclitaxel

First

reports

of

bevacizumab

Positive

evidence

for weekly

paclitaxel

in first line

Key

advances

in chemo-

therapy

1970 1980 1990 2000

First

use of

oral

PARPi

2010

From Edmonson JH. Gynecol Oncol 2000; 79:145–146

Empirically derived cytoablative chemotherapy

Genetically specific molecular therapy

1960 1970 1980 1990 2000 2010 2020 2030 2040

Year

0

20

40

60

80

100

% o

f th

erap

y

Angiogenesis: A Complex Process

FGF, fibroblast growth factor; PDGF, platelet-derived growth factor

Adapted from: Dudley AC, et al. In: Markland FS, et al, eds. Tumor angiogenesis: From molecular mechanisms to

targeted therapy. Weinheim, Germany: Wiley-VCH; 2010: 22.

4th Ovarian Cancer Consensus Conference

25–27 June 2010

UBC Life Sciences Institute, Vancouver, BC

B-2: What are the promising targets for future therapeutic approaches?

• The most promising targets in clinical trials are angiogenesis and

homologous recombination deficiency

• To select patients for trials investigating these targets, predictive

biomarkers are required. Understanding mechanisms of resistance is a

priority

• Other promising targets currently being studied based on ovarian cancer

biology include:

– PI3-Kinase and Ras/Raf pathways

– Folate receptor

• Immune targets/cytokines, Notch/hedgehog, IGF merit further investigation

• Targeted agents should be studied both as single agents and in combination

based on appropriate preclinical data

Significant ongoing interest in angiogenesis

inhibition in ovarian cancer

Agent Trial Setting Regimen Estimated

enrolment

Estimated primary

completion date

Pazopanib AGO-OVAR16

(NCT00866697)

Front-line Pazopanib monotherapy versus

placebo 900 ASCO 2013

BIBF 1120 AGO-OVAR12

(NCT01015118)

Front-line BIBF 1120 in combination with CP

compared to placebo plus CP 1300 ESMO 2013

AMG 386

TRINOVA-1

(NCT01204749) Recurrent (partially

platinum sensitive

or platinum

resistant)

AMG 386 or placebo, in combination

with weekly paclitaxel 900 ESGO 2013

TRINOVA-2

(NCT01281254)

Pegylated liposomal doxorubicin

(PLD) plus AMG 386 or placebo 380 April 2014

TRINOVA-3

(NCT01493505)

Front-line AMG 386 with CP followed by single-

agent AMG 386 2000 May 2016

Bevacizumab

AGO-OVAR 17

(BOOST;

NCT01462890)

Front-line

Carboplatin/paclitaxel + bevacizumab

(15 vs 30 months) 800 November 2018

GOG-0262

(NCT01167712)

CP (qw vs q3w) + bevacizumab 625 February 2012

GOG-0252

(NCT00951496)

IV vs IP chemotherapy +

bevacizumab 1500 January 2016

GOG-0213

(NCT00565851)

Recurrent (platinum

sensitive)

CP + bevacizumab 660 December 2009

ANTIANGIOGENESIS Y CANCER DE OVARIO 2013

• BEVACIZUMAB. – FRONT-LINE

• GOG-218 NEJM • ICON-7 NEJM. OS ASGO

– PS RELAPSE • OCEAN JCO

– PR RELAPSE • AURELIA In Press

• PAZOPANIB – FRONT-LINE ASCO-13 (In Press)

• NINDETANIB – FRONT-LINE ESGO-13

• TREBANANIB – PR/PPS TRINOVA-1 ESGO-13 (In Press)

• CEDIRANIB – PS ICON-6 ESGO-13 (In Press)

Presented by Monk BJ at the European Society of Gynecologic Oncology 2013

Angiogenesis as a Target in

Ovarian Cancer • Anti-vascular endothelial growth factor (VEGF) therapy

improves progression-free survival (PFS)

• GOG 218 Front-line: Bevacizumab

HR = 0.72; 95% CI, 0.63–0.821

• ICON 7 Front-line: Bevacizumab

HR = 0.81; 95% CI, 0.70–0.942

• AGO-OVAR12 Front-line: Nintedanib

HR = 0.84; 95% CI, 0.72, 0.983

• AGO-OVAR16 Maintenance: Pazopanib

HR = 0.77; 95% CI, 0.64–0.914

• AURELIA Platinum-resistant, recurrent / 1 or 2 prior regimens: Bevacizumab

HR = 0.48; 95% CI, 0.38–0.605

• OCEANS Platinum-sensitive, recurrent / 1 prior regimen: Bevacizumab

HR = 0.53; 95% CI, 0.41–0.706

• ICON6 Platinum-sensitive, recurrent / 1 prior regimen: Cediranib

HR = 0.57; 95% CI, 0.44–0.747

HR = hazard ratio; 95% CI = confidence interval

1. Burger RA et al. N Engl J Med. 2011;365:2473‒2483.

2. Perren TJ et al . N Engl J Med. 2011;365:2484‒2496.

3. du Bois A et al. J Clin Oncol. 2013;31(18suppl):LBA5503.

4. du Bois A et al. LBA ESGO 2013 Liverpool, UK

5. Pujade-Lauraine E et al. J Clin Oncol. 2012;30(18suppl):LBA5002.

6. Aghajanian C et al. J Clin Oncol. 2012;30:2039‒2045.

7. Ledermann JA et al . Eur J Cancer. 2013;49(suppl):LBA

ANTIANGIOGENESIS Y CANCER DE OVARIO 2013

– MAS DE 5000 pacientes tratDOS EN ENSAYOS DE PRIMERA LÍNEA

– TODOS POSITIVOS PARA PFS

– ALGUNO PARA SUBGRUPOS OS

– EXPLICACION TRASLACIONAL PENDIENTE

It’s All About the Choices…