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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
  1. Anca Chelariu-Raiciu1,2,
  2. Fabian Trillsch1,2,
  3. Phillip Harter3,
  4. Ralf Strobl4,5,
  5. Jalid Sehouli6,7,
  6. Pauline Wimberger8,
  7. Holger Bronger9,
  8. Catherine Shannon10,
  9. Claudia Lefeuvre11,
  10. Joern Rau12,
  11. Lars Hanker13,
  12. Stephan Polterauer14,
  13. Frederik Marmé15,
  14. Ahmed El-Balat16,17,
  15. Martin R Stockler18,
  16. Nikolaus De Gregorio19,
  17. Ros Glasspool20,
  18. Sven Mahner1,2,
  19. Alain Lortholary21 and
  20. Jacobus Pfisterer22
  1. 1AGO study group and Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany
  2. 2German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
  3. 3AGO study group and Ev. Kliniken Essen Mitte, Essen, Germany
  4. 4AGO study group and Institute for Medical Information Processing, Biometrics and Epidemiology, Faculty of Medicine, LMU Munich, Munich, Germany
  5. 5German Center for Vertigo and Balance Disorders, LMU Munich, Munich, Germany
  6. 6AGO study group and Department of Gynecology with Center for Oncological Surgery Charité – Universitätsmedizin Berlin, Berlin, Germany
  7. 7Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie (NOGGO e.V.), Munich, Germany
  8. 8AGO study group and Gynecology and Obstetrics, Technische Universitaet Dresden Medizinische Fakultat Carl Gustav Carus, Dresden, Germany
  9. 9AGO study group and Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany
  10. 10ANZGOG and Mater Cancer Care Centre, South Brisbane, Queensland, Australia
  11. 11GINECO and Centre Eugène Marquis, Rennes, France
  12. 12AGO study group and Coordinating Centre for Clinical Trials, Philipps-Universität Marburg, Marburg, Germany
  13. 13AGO study group and Department of Obstetrics and Gynecology, University Hospital of Schleswig Holstein, Lübeck, Germany
  14. 14AGO-Austria and Department of Obstetrics and Gynecology, Division General Gynecology and Gynecologic Oncology, Medical University of Vienna, Vienna, Austria
  15. 15AGO study group and Medical Faculty Mannheim, Heidelberg University, University Hospital Mannheim, Mannheim, Germany
  16. 16AGO study group and Department of Gynecology and Obstetrics, University Clinic Frankfurt, Goethe-University, Frankfurt Am Main, Germany
  17. 17Spital Uster, Women’s Hospital, Uster, Switzerland
  18. 18NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia
  19. 19AGO study group and Klinikum am Gesundbrunnen, SLK-Kliniken Heilbronn GmbH, Heilbronn, Germany
  20. 20SGCTG and University of Glasgow, Glasgow, UK
  21. 21GINECO and Medical Oncology, Hôpital Privé du Confluent, Nantes, France
  22. 22AGO study group and Gynecologic Cancer Center, Kiel, Germany


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.

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