1. State of the Art in Ovarian cancer Jan B. Vermorken, MD, PhD Department of Medical Oncology Antwerp University Hospital Edegem, Belgium 3rd EASO Masterclass in Clinical Oncology Amman, 2011

3. Five-year Survival in Ovarian Cancer 30 years of experience Vol. Year Cases Ia IV Overall (n) % 16 1963-68 4588 66.7 5.0 27.3 19 1976-78 6724 72.3 4.5 29.8 21 1982-86 10912 82.3 8.0 35.0 23 1990-92 7059 83.5 11.1 41.6 25 1996-98 4116 89.3 13.4 46.4 26* 1999-01 4911 89.3 18.6 49.7 Int. J Gynecol Obstet 2006 (Suppl 1)

5. Epithelial Ovarian Cancer Milestones http://ctep.cancer.gov/resources/gcig/index.html

9. Optimal First-line Chemotherapy in ADOVCA: Historical Perspective Alkylating Cisplatin Carboplatin Paclitaxel Agents     Doxorubicin topotecan?, LPD? gemcitabine? Epirubicin

15. Targeted Therapies in Ovarian Cancer Target Drug(s) ErbB kinases Gefitinib, erlotinib, lapatinib, canertinib, cetuximab, pertuzumab, matuzumab, trastuzumab MUC1 / PEM Pemtumomab MUC16 (CA 125) Oregovomab mTOR / AKT Temsirolimus, everolimus, deforolimus Apoptosis pathway AEG35156, OGX-011 Angiogenesis Bevacizumab, sunitinib, sorafenib, pazopanib, cediranib, vatalanib Endothelial cells Combretastatin, Oxi4503 Matrix metalloproteinases BAY 12-9566, marimastat

19. ICON-7: PFS http://www.ctu.mrc.ac.uk/icon7/content_pages/documents/ICON7_%20ESMO%20Presidential%20Presentation.pdf Accessed 15 October 2010 Academic analysis

21. Kristensen G. et al, ASCO 2011, abstract #LBA5006

22. Kristensen G. et al, ASCO 2011, abstract #LBA5006

27. When to Treat? Harries and Gore, 2002

28. Trial Design Ovarian cancer in complete remission after first-line platinum based chemotherapy and a normal CA125 CA125>2 x upper limit of normal RANDOMIZED Early treatment Clinician and patient informed Delayed treatment Clinician not informed , treatment delayed until clinically indicated REGISTER Blinded CA125 measured every 3 months Rustin GJ et al, Lancet 2010; vol 376: 1155-1163

29. Overall Survival HR=1.00 (95%CI 0.82-1.22) p=0.98 Early Delayed Abs diff at 2 years= 0.1% (95% CI diff= -6.8, 6.3%) Rustin GJ et al, Lancet 2010; vol 376: 1155-1163

30. Time from Randomisation to First Deterioration in Global Health Score (or death) Proportion alive without deterioration in GHS Number at risk Rustin GJ et al, Lancet 2010; vol 376: 1155-1163

36. Main reason for discontinuation of Bev = PD

37. CALYPSO (n=973 patients) q 4 wks q 3 wks PLD 30 mg/m², d1 Carbo AUC 5 PACL 175 mg/m², d1 Carbo AUC 5, d1 Efficacy* PFS 11.3 mo PFS 9.4 mo* Toxicity PLT, HFS, nausea** mucositis ANC, alopecia, HSR** sensory neuropathy *HR 0.82 (95% CI 0.72-0.94), p=0.005 **p<0.01 Pujade-Laurain et al, J Clin Oncol 2010; 28: 3323-3329

41. Monk BJ et al, J Clin Oncol 2010; 28(19):3107-14.

42. An Open-label Multicenter Randomized Phase 3 Study Comparing DOXIL/CAELYX and Trabectedin with DOXIL/CAELYX Alone in Advanced ROC Monk BJ et al, submitted

44. Phase 2 Randomized Placebo-controlled Study of Olaparib in Pts with Platinum-Sensitive relapsed Serous OC Ledermann J et al (# 5003) n = 265