1. OCEANS: A Randomized, Double- Blinded, Placebo-Controlled Phase III Trial of Chemotherapy with or without Bevacizumab (BEV) in Patients with Platinum- Sensitive Recurrent Epithelial Ovarian (EOC), Primary Peritoneal (PPC), or Fallopian Tube Cancer (FTC) Aghajanian C et al. Proc ASCO 2011;Abstract LBA5007.

2. CG x 6-10 cycles + PL q3wk, until progression Accrual: 484 (Closed) Eligibility Platinum-sensitive recurrent OC (epithelial ovarian, primary peritoneal or fallopian tube cancer) Measurable disease No prior chemotherapy for recurrent OC No prior bev R Aghajanian C et al. Proc ASCO 2011;Abstract LBA5007. C = carboplatin AUC4; G = gemcitabine 1,000 mg/m 2, d1 & 8; PL = placebo; bev = bevacizumab CG x 6-10 cycles + bev q3wk, until progression Oceans Study Schema

3. Characteristic CG + PL (n = 242) CG + bev (n = 242) Median age, years6160 Age ≥ 65 years, %3835 Histologic subtype, % Serous Mucinous/clear cell Other 84 3 14 78 5 17 Platinum-free interval, % 6-12 months >12 months 42 58 41 59 Cytoreductive surgery for recurrent disease 1012 Aghajanian C et al. Proc ASCO 2011;Abstract LBA5007. OCEANS: Patient Characteristics

4. OCEANS: Response Patients, % CG + PL (n = 242) CG + bev (n = 242) Hazard ratiop-value Objective response57%78% NR<0.0001 Complete response9%17% Partial response48%61% Median duration of response (n = 139, 190) 7.4 mo10.4 mo0.534<0.0001 Aghajanian C et al. Proc ASCO 2011;Abstract LBA5007.

5. OCEANS: Progression-Free Survival CG + PL (n = 242) CG + bev (n = 242) Events, n (%)187 (77)151 (62) Median PFS, months (95% CI) 8.4 (8.3–9.7) 12.4 (11.4–12.7) Stratified analysis HR (95% CI) Log-rank p-value 0.484 (0.388–0.605) <0.0001 Aghajanian C et al. Proc ASCO 2011;Abstract LBA5007.

6. OCEANS: Select Adverse Events Patients, % CG + PL (n = 233) CG + bev (n = 247) Neutropenia, Grade ≥35658 Febrile neutropenia, Grade ≥322 Hypertension, Grade ≥3<117 Fistula/abscess, all grades<12 Proteinuria, Grade ≥319 GI perforations00 Reversible leukoencephalopathy syndrome 01 Wound-healing complication, Grade ≥301 Aghajanian C et al. Proc ASCO 2011;Abstract LBA5007.

7. Author Conclusions Bevacizumab/carboplatin/gemcitabine followed by bevacizumab until progression provides clinically meaningful benefit compared to chemotherapy alone in recurrent OC –Improved PFS: 12.4 months vs 8.4 months; HR = 0.484 (p < 0.0001) –Improved ORR: 78% vs 57% (p < 0.0001) –Improved DOR: 10.4 months vs 7.4 months Safety data are consistent with the profile for bevacizumab This regimen should be considered a new option for recurrent platinum-sensitive OC Aghajanian C et al. Proc ASCO 2011;Abstract LBA5007.

8. Investigator Commentary: Results from the OCEANS Phase III Trial The OCEANS study built in concurrent chemotherapy with bevacizumab in a population that was platinum sensitive with recurrent disease. This study did provide bevacizumab until progression as maintenance and showed a significant separation of the curves from the beginning of therapy, which continued for a long time. The hazard ratio of about 0.48 was statistically significant, and I believe that continuing with bevacizumab until progression probably maintained disease control for a longer period. What seems to be emerging is that continuing with bevacizumab until progression would make sense in patients who are at high risk of having recurrent disease over a short period. Amit M Oza, MD The data in ovarian cancer have continued to accumulate in a positive way. The OCEANS study showed a substantial advantage in time to progression in the patients who had received bevacizumab with carboplatin and gemcitabine, as opposed to the carboplatin, gemcitabine and placebo group, and this seems to be a positive option. David R Spriggs, MD