¿Cómo Incorporar la Terapia Antiangiogénica en el Cáncer de Ovario… · XIV Congreso Nacional...
Transcript of ¿Cómo Incorporar la Terapia Antiangiogénica en el Cáncer de Ovario… · XIV Congreso Nacional...
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¿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
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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
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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
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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.
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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
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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
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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)
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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
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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
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It’s All About the Choices…