Upfront Surgery vs Neoadjuvant Chemotherapy Patients closed / 550 Leading EORTC Participating NCIC CTG Presentated at IGCS 2008 EORTC 55971

Tarceva consolidation 2 years Primary Chemotherapy Control Patients closed / 835 Leading EORTC Participating AGO-AUSTRIA, ANZGOG, GINECO, MRC/NCIC, MANGO Tarceva Trial EORTC 55041

TC ± BEVACIZUMAB Patients closed / 1520 Leading MRC/NCRI Participating NCIC CTG, AGO OVAR, GINECO, GEICO EORTC, ANZGOG, NSGO ICON-7

CT vs CT + Bevacizumab Placebo vs CT + Bevacizumab concurrent and extended Patients closed / 1800 Leading GOG Participating ECOG, NCCTG, NSABP, SWOG GOG 218

10 Phase III Trial of Bevacizumab in the Primary Treatment of Advanced Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer: A Gynecologic Oncology Group (GOG) Study R.A. Burger, 1 M.F. Brady, 2 M.A. Bookman, 3 J.L. Walker, 4 H.D. Homesley, 5 J. Fowler, 6 B.J. Monk, 7 B.E. Greer, 8 M. Boente, 9 S.X. Liang 10 1 Fox Chase Cancer Center, Philadelphia, PA; 2 Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY; 3 University of Arizona Cancer Center, Tucson, AZ; 4 University of Oklahoma Health Sciences Center, Oklahoma City, OK; 5 Brody School of Medicine, Greenville, NC; 6 James Cancer Hospital at the Ohio State University, Hilliard, OH; 7 University of California, Irvine Medical Center, Orange, CA; 8 Seattle Cancer Care Alliance, Seattle, WA; 9 Minnesota Oncology and Hematology, Minneapolis, MN; 10 State University of New York at Stony Brook, Stony Brook, NY, USA

GOG-0218: Investigator-Assessed PFS Arm I CP (n=625) Arm II CP + BEV (n=625) Patients with event, n (%) 423 (67.7) 418 (66.9) Median PFS, months Stratified analysis HR (95% CI) (0.759–1.040) One-sided p-value (log rank)0.080* + BEV (Arm II) CP (Arm I) *p-value boundary = BEV → BEV maintenance (Arm III) Proportion surviving progression free Months since randomization Arm III CP + BEV  BEV (n=623) 360 (57.8) (0.625–0.824) <0.0001* 11

Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer Optimal and Suboptimal Disease (through April 2011) Optimal and Suboptimal Disease (through April 2011) Primary Endpoint: PFS Primary Endpoint: PFS GOG0252: IP Therapy Open:27-Jun-09 Closed:(ongoing) Target Accrual:1250 pts Walker J. for GOG, pending Carboplatin AUC=6 (IV) Paclitaxel 80 mg/m 2 IV (d1,8,15) Bevacizumab (C2-6) Cisplatin 75 mg/m 2 (IP) Paclitaxel 135 mg/m 2 (d1, 3h) Paclitaxel 60 mg/m 2 (d8, IP) Bevacizumab (C2-6) I III II Carboplatin AUC=6 (IP) Paclitaxel 80 mg/m 2 (d1,8,15) Bevacizumab (C2-6) Bevacizumab q21d x 16 Bevacizumab Bevacizumab

Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer Suboptimal residual disease Suboptimal residual disease Primary Endpoint: PFS Primary Endpoint: PFS GOG0262: Dose-Dense Integration Open:27-SEP-10 Closed:--- Target Accrual:1100 pts Chan J. for GOG, pending Carboplatin AUC=6 Paclitaxel 80 mg/m 2 (d1,8,15) +/- Bevacizumab (C2-6) $ I II Bevacizumab q21d $ Bevacizumab Carboplatin AUC=6 Paclitaxel 175 mg/m 2 (d1) +/- Bevacizumab (C2-6) $ $ Use of Bevacizumab to be determined by patient and physician choice prior to randomization physician choice prior to randomization

Recurrent epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer Platinum-Free Interval stratified 6-12 vs >12 months Industry-sponsored multicenter phase II amended to phase III Primary Endpoint: PFS with RECIST Secondary Endpoints: OS, GI perforation event rate OCEANS: CG +/- Bevacizumab x 6 Gemcitabine 1000 mg/m 2 d1,8 Carboplatin AUC=4.0 d1 Bevacizumab 15 mg/kg IV d1 II x 6 I Gemcitabine 1000 mg/m 2 d1,8 Carboplatin AUC=4.0 d1 Placebo IV d1 Bevacizumab q21d (until PD) Open:Apr-07 Closed:Jan-10 Target Accrual:483 pts Aghajanian C, et al. (under analysis) Placebo q21d (until PD)

MaximalSecondaryCytoreduction No Secondary Surgery Epithelial Ovarian, Fallopian, or Peritoneal Cancer Epithelial Ovarian, Fallopian, or Peritoneal Cancer One prior therapy, Platinum-free interval > 6 months One prior therapy, Platinum-free interval > 6 months Primary Endpoint: OS Primary Endpoint: OS Open:06-Dec-07 Closed:Ongoing Target Accrual:660 pts I II GOG 0213: Secondary Cytoreduction Coleman, et al Carboplatin AUC=5 Paclitaxel 175 mg/m 2 (No further therapy) Carboplatin AUC=5 Paclitaxel 175 mg/m 2 Bevacizumab 15 mg/kg (Until progression) A B R1 Not Surgical Candidate III x 6-8 R2

Epithelial Ovarian or Primary Peritoneal Cancer Epithelial Ovarian or Primary Peritoneal Cancer Optimal or Suboptimal Cytoreduction Optimal or Suboptimal Cytoreduction Clinical CR with normal CA125, no symptoms, normal CT Clinical CR with normal CA125, no symptoms, normal CT Primary Carboplatin and Paclitaxel (or Docetaxel), 5-6 cycles Primary Carboplatin and Paclitaxel (or Docetaxel), 5-6 cycles GOG212: Ovarian Maintenance x 12 I PG-Paclitaxel 175 mg/m 2 (15 m), q28d x 12 II Paclitaxel 175 mg/m 2 (3 h), q28d IIIObservation Open:Mar-05 Closed:--- Target Accrual:1550 pts (3.5 Y+) Markman, et al. for GOG Primary Rx: Carboplatin and Taxane (5-6 Cycles)

C ALYPSO Published Ahead of Print on May 24, 2010

Carbo Paclitaxel +/- Gemcitabine Patients closed 1742 Leading AGO-OVAR Participating GINECO, NSGO, AGO-OVAR-9

Carbo Flat Dosing vs Intrapatient Dose Escalation Patients closed 932 Leading SGCTG Participating ANZGOG Manuscript in preparation SCOTROC 4

Carbo Topo vs Chemo (CT or CG) in recurrent Platinum-sensitive ovarian cancer Patients closed 550 Leading NOGGO/AGO-OVAR Participating AGO-AUSTRIA, GEICO HECTOR

Evaluation of predictive factors for complete resection in platinum-sensitive recurrent ovarian cancer Patients closed/412 Leading AGO-OVAR ParticipatingAGO-AUSTRIA, MITO, selected Canadian+Australian centers Report IGCS 2008, resubmitted AGO-OVAR-OP.2 DESKTOP II

Pazopanib consolidation 1 yr First Line Chemotherapy Control Patients 941 / 900 Leading AGO-OVAR Participating AGOAustria, ANZGOG, BGOG, GEICO, GINECO, ICORG, JGOG, KGOG, MANGO, MITO, NSGO, US-Sites: California Consortium, NY GOG, SWOG AGO-OVAR 16 Amendment: 2 years of consolidation

Carbo Paclitaxel +/- BIBF 1120 (Vargatef) Patients 525 / 1300 (2:1 random) Leading AGO-OVAR Participating AGO-Austria, BGOG, GINECO, MANGO, MITO, NSGO, US Oncology AGO-OVAR-12

R System. Lymphadenectomy pelvic para-aortic no Lymphadenectomy epithelial invasive ovarian cancer FIGO IIB - IV ECOG 0/1 and no CI against LNE no visible extra- and intra-abdominal tumor residuals no bulky lymph nodes Endpoints: OS, PFS, QoL Strata: centre, PS,age Lymphadenectomy In Ovarian Neoplasms AGO – OVAR OP.3 (LION) 284/640 Supported by Deutsche Forschungsgemeinschaft

CT vs CDDP + Irinotecan Patients 597/662 Leading JGOG ParticipatingGINECO, GOG, KGOG, MITO, SGCTG JGOG-3017 Clear Cell Carcinoma

C (3w, IV) T (1w, IV) vs C (3w, IP) T (1w, IV) Patients 3/746 Leading JGOG Participating? JGOG-3019 iPocc

Weekly CT vs 3-weekly CT (QoL) Patients 315 / 650 Leading MITO Participating MaNGO MITO-7

LipDox vs CT cross-over in 6-12 m platinum-free interval Patients 72 / 253 Leading MITO Participating MaNGO, AGO-OVAR MITO-8

Bevacizumab plus chemotherapy vs chemotherapy alone in patients with platinum-resistant EOC Patients 226 / 332 Leading GINECO Participating AGO-OVAR, GEICO, MITO, NSGO, BGOG, DGOG A URELIA

Dipartimento di Oncologia - Istituto “Mario Negri” - Milano INOVATYON Randomization (strata: ECOG, Measurable disease, PFI) PLD 30 mg/m2 1 hour i.v. + Carboplatin AUC min i.v. on day 1 q4weeks Up to 6 cycles or progression Relapsed ovarian cancer with platinum-free interval (PFI) of 6-12 months PLD 30 mg/m2 1 hour i.v. + Trabectedin 1.1 mg/m2 3 hoour i.v. on day 1 q3weeks Up to 6 cycles or progression 3rd line chemotherapy: at investigator discretion 3rd line chemotherapy: platinum rechallenge

Cytoreductive surgery vs NO surgery in platinum-sensitive recurrent EOC Patients 3 / 385 activated July 1 Leading AGO-OVAR Participating? AGO-OVAR-OP.4 DESKTOP III

oxaliplatin + capecitabine ± bevacizumab vs carboplatin + paclitaxel ± bevacizumab Patients 0/332 Leading NCRI/SGCTG GOG Participating AGO OVAR, GINECO, MaNGO, NSGO, KGOG MucinousEOC

Patients 1485 Leading MRC Participating?? ICON 8 C 3w P 3w vs C 3w P 1w vs C 1w P 1w

IP/IV Platinum/P vs IV CP optimally debulked following NACT Patients 0 / 780 Leading NCIC CTG ParticipatingGEICO, NCRI, SWOG NCIC CTG OV.21

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