Cómo Incorporar la Terapia Antiangiogénica en el Cáncer de Ovario? XIV Congreso Nacional Salamanca Octubre de 2013 SESION CONTROVERSIA-1 15,45-17H

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1 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

2 Progress in the Management of Ovarian Cancer: Evolution Over 40 Years Five-year survival 15% 30% 40% 50%? Key advances in chemotherapy First use of cisplatin First use of carboplatin First use of paclitaxel First reports of bevacizumab First use of oral PARPi Positive evidence for weekly paclitaxel in first line

3 % of therapy Empirically derived cytoablative chemotherapy Genetically specific molecular therapy Year From Edmonson JH. Gynecol Oncol 2000; 79:

4 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.

5 4th Ovarian Cancer Consensus Conference 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

6 Significant ongoing interest in angiogenesis inhibition in ovarian cancer Agent Trial Setting Regimen Estimated enrolment Pazopanib AGO-OVAR16 (NCT ) Front-line Estimated primary completion date Pazopanib monotherapy versus 900 ASCO 2013 placebo BIBF 1120 AGO-OVAR12 (NCT ) Front-line BIBF 1120 in combination with CP 1300 ESMO 2013 compared to placebo plus CP AMG 386 TRINOVA-1 (NCT ) TRINOVA-2 (NCT ) Recurrent (partially platinum sensitive or platinum resistant) AMG 386 or placebo, in combination 900 ESGO 2013 with weekly paclitaxel Pegylated liposomal doxorubicin April (PLD) plus AMG 386 or placebo TRINOVA-3 (NCT ) Front-line AMG 386 with CP followed by singleagent AMG May AGO-OVAR 17 (BOOST; NCT ) Carboplatin/paclitaxel + bevacizumab November (15 vs 30 months) Bevacizumab GOG-0262 (NCT ) GOG-0252 (NCT ) Front-line CP (qw vs q3w) + bevacizumab 625 February 2012 IV vs IP chemotherapy + January bevacizumab GOG-0213 (NCT ) Recurrent (platinum sensitive) CP + bevacizumab 660 December 2009

7 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)

8 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, ICON 7 Front-line: Bevacizumab HR = 0.81; 95% CI, AGO-OVAR12 Front-line: Nintedanib HR = 0.84; 95% CI, 0.72, AGO-OVAR16 Maintenance: Pazopanib HR = 0.77; 95% CI, AURELIA Platinum-resistant, recurrent / 1 or 2 prior regimens: Bevacizumab HR = 0.48; 95% CI, OCEANS Platinum-sensitive, recurrent / 1 prior regimen: Bevacizumab HR = 0.53; 95% CI, ICON6 Platinum-sensitive, recurrent / 1 prior regimen: Cediranib 1. Burger RA et al. N Engl J Med. 2011;365: Perren TJ et al. N Engl J Med. 2011;365: du Bois A et al. J Clin Oncol. 2013;31(18suppl):LBA du Bois A et al. LBA ESGO 2013 Liverpool, UK 5. Pujade-Lauraine E et al. J Clin Oncol. 2012;30(18suppl):LBA Aghajanian C et al. J Clin Oncol. 2012;30: Ledermann JA et al. Eur J Cancer. 2013;49(suppl):LBA HR = 0.57; 95% CI, Presented by Monk BJ at the European Society of Gynecologic Oncology 2013 HR = hazard ratio; 95% CI = confidence interval

9 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

10 It s All About the Choices