803 Efficacy and Safety of Bevacizumab Following Prior Anti-Angiogenic Treatment in Patients with Second-Line Platinum- Based Chemotherapy in Recurrent Ovarian Cancer – a Subgroup Analysis of the AGO-OVAR 2.21 Phase III Trial

Introduction/Background AGO-OVAR 2.21 is the first phase III trial in recurrent ovarian cancer that compared two bevacizumab-containing combination chemotherapy regimens independent of prior anti-angiogenic therapy. As safety and efficacy data on bevacizumab re-challenge is limited, this present exploratory analysis focuses on patients with prior anti-angiogenic therapy. Methodology Clinical data, medical history or ongoing side effects from prior anti-angiogenic therapy (t0), side effects reported during the trial (t1), and response to therapy, was collected. Clinical characteristics were compared for patients with prior anti-angiogenic therapy versus controls with no prior anti-angiogenic therapy with chi squared testing. Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models, were used for the time to event analyses. Results Of 682 enrolled patients 324 (47.5%) had previously been treated with anti-angiogenic therapy. Overall relative risk (RR) at t1 for any bevacizumab-associated side effects, including arterial hypertension, thrombosis, proteinuria, and fistula was 44.3% vs 60.3% (RR=0.73, P<0.0001) in patients following prior anti-angiogenic therapy compared to anti-angiogenic-naïve patients (patients with a prior diagnosis of blood pressure, proteinuria, thrombosis, and fistula at t0 were excluded). Similarly, relative risk was comparable for specific subgroups of side effects with arterial hypertension (30.8% vs 49.3%, RR=0.62; P<0.0001), proteinuria (17.5% vs 23.7%, RR=0.74; P=0.061), thrombosis (2.5% vs 4.9%, RR=0.51; P=0.157), and fistula (0.6% vs 1.1%, RR=0.55; P=0.766). PFS was shorter among patients with prior exposure to anti-angiogenic therapy than controls: medians 11.0 vs 14.2 months, (hazard ratio 1.60, 95%- confidence interval 1.35 to 1.89, P<0.0001). Conclusion In this explorative analysis of patients with and without previous anti-angiogenic therapy undergoing treatment with a bevacizumab-containing combination chemotherapy, we observed that safety profile was within the expected range. Although prognostic impact appears to be lower in patients with prior anti-angiogenic exposure compared to anti-angiogenic drug-naïve patients, overall efficacy from bevacizumab with chemotherapy in platinum-eligible disease was demonstrated independent from prior treatment. Disclosures HB: Research Funding: GSK, AstraZeneca, Merck, Sharp & Dohme (MSD). Consulting/Ad Bds: GSK, AstraZeneca, Merck, Sharp & Dohme (MSD) JS: Research Funding: Institution: AZ, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, Roche. Consulting/Ad Bds: AZ, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, J&J, Roche, Ingress Health, Riemser, Sobi, GSK, Novartis; Honoraria: AZ, Eisai, Clovis Oncology, Olympus Medical Systems, J&J, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GSK, Bayer; Travel, Accommodations, Expenses: AZ, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, Olympus; AL: Honoraria: MSD, AZ, Tesaro, Clovis Oncology FT: Research Funding: AstraZeneca, ImmunoGen, SAGA diagnostics; Honoraria: AstraZeneca, Clovis, Eisai, GSK, MSD, Roche PH: Research Funding: Astra Zeneca, Roche, GSK, Genmab, Immunogen, Seagen, Clovis, Novartis (all institutional); Consulting/Ad Bds: Amgen, Astra Zeneca, Clovis, Eisai, Immunogen, GSK, Exscientia, Mersana, Miltenyi, MSD, Novartis, Roche, Stryker, Zai Lab; Travel support: Astra Zeneca. RG: Research Funding: Clovis; Honoraria: GSK, Clovis. PW: Research Funding:: Roche; Honoraria: Roche. JP: Research Funding: Roche, GSK. Honoraria: Medupdate, Decision Resources, Simon-Kucher and Partners, Juniper, Bionest Partner, Vox Bio, Axiom Healthcare Strategies, Prosapient, Lilly, Sai Med Partners. Travel: Roche. SM: Research funding, honorary, or travel expenses from and is a member of the advisory board of AbbVie, AstraZeneca, Clovis, Eisai, GlaxoSmithKline, Hubro, Medac, MSD, Novartis, Nykode, Olympus, PharmaMar, Pfizer, Roche, Sensor Kinesis, Teva, and Tesaro. FM reports institutional research funding from Roche, Novartis, AstraZeneca, GSK and Tesaro, MED, Clovis, Vaccibody, Gilead Sciences, and Eisai; consulting fees from AstraZeneca, GSK and Tesaro, Pfizer, Eisai, Gilead Sciences, Vaccibody, and GenomicHealth; honoraria from AstraZeneca, Clovis, GSK and Tesaro, Eli Lilly, Novartis, Pfizer, Roche, Myriad Genetics, PharmaMar, Eisai, MSD, Immunomedics and Gilead Sciences, Pierre-Fabre, Agendia, Genomic Health, and Seattle Genetics; support for meeting attendance and travel from Pfizer, Roche, and AstraZeneca; and participation on a data safety monitoring board. Ahmed.