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%? 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 1970 1980 1990 2000 2010
% of therapy 100 80 60 Empirically derived cytoablative chemotherapy Genetically specific molecular therapy 40 20 0 1960 1970 1980 1990 2000 2010 2020 2030 2040 Year From Edmonson JH. Gynecol Oncol 2000; 79:145 146
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 Pazopanib AGO-OVAR16 (NCT00866697) Front-line Estimated primary completion date Pazopanib monotherapy versus 900 ASCO 2013 placebo BIBF 1120 AGO-OVAR12 (NCT01015118) Front-line BIBF 1120 in combination with CP 1300 ESMO 2013 compared to placebo plus CP AMG 386 TRINOVA-1 (NCT01204749) TRINOVA-2 (NCT01281254) Recurrent (partially platinum sensitive or platinum resistant) AMG 386 or placebo, in combination 900 ESGO 2013 with weekly paclitaxel Pegylated liposomal doxorubicin April 2014 380 (PLD) plus AMG 386 or placebo TRINOVA-3 (NCT01493505) Front-line AMG 386 with CP followed by singleagent AMG May 2016 2000 386 AGO-OVAR 17 (BOOST; NCT01462890) Carboplatin/paclitaxel + bevacizumab November 2018 800 (15 vs 30 months) Bevacizumab GOG-0262 (NCT01167712) GOG-0252 (NCT00951496) Front-line CP (qw vs q3w) + bevacizumab 625 February 2012 IV vs IP chemotherapy + January 2016 1500 bevacizumab 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)
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 0.82 1 ICON 7 Front-line: Bevacizumab HR = 0.81; 95% CI, 0.70 0.94 2 AGO-OVAR12 Front-line: Nintedanib HR = 0.84; 95% CI, 0.72, 0.98 3 AGO-OVAR16 Maintenance: Pazopanib HR = 0.77; 95% CI, 0.64 0.91 4 AURELIA Platinum-resistant, recurrent / 1 or 2 prior regimens: Bevacizumab HR = 0.48; 95% CI, 0.38 0.60 5 OCEANS Platinum-sensitive, recurrent / 1 prior regimen: Bevacizumab HR = 0.53; 95% CI, 0.41 0.70 6 ICON6 Platinum-sensitive, recurrent / 1 prior regimen: Cediranib 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 HR = 0.57; 95% CI, 0.44 0.74 7 Presented by Monk BJ at the European Society of Gynecologic Oncology 2013 HR = hazard ratio; 95% CI = confidence interval
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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