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Clinical trial
AGO-OVAR 28/ENGOT-ov57. Niraparib alone versus niraparib in combination with bevacizumab in patients with carboplatin-taxane-based chemotherapy in advanced ovarian cancer: a multicenter randomized phase III trial
  1. Florian Heitz1,2,
  2. Christian Marth3,
  3. Stéphanie Henry4,
  4. Alexander Reuss5,
  5. David Cibula6,
  6. Lydia Gaba Garcia7,
  7. Nicoletta Colombo8,9,
  8. Barbara Schmalfeld10,
  9. Nikolaus de Gregorio11,
  10. Pauline Wimberger12,
  11. Annette Hasenburg13,
  12. Jalid Sehouli14,
  13. Martina Gropp-Meier15,
  14. Philip C Schouten16,
  15. Eric Hahnen17,
  16. Jan Hauke16,
  17. Sandra Polleis18 and
  18. Philipp Harter1
  1. 1AGO Studygroup and Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte Evangelische Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany
  2. 2Department for Gynecology with the Center for Oncologic Surgery Charité Campus Virchow-Klinikum, Berlin Institute of Health, Berlin, Germany
  3. 3Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria
  4. 4CHU UCL Namur Site Sainte Elisabeth, Namur, Belgium
  5. 5Coordinating Centre for Clinical Trials, Philipps-Universität Marburg, Marburg, Germany
  6. 6CEEGOG & Department of Obstetrics and Gynecology, First Medical Faculty of the Charles University, Prague, Czech Republic
  7. 7Department of Medical Oncology, Hospital Clinic Barcelona, Barcelona, Spain
  8. 8Medical Gynecologic Oncology Unit, University of Milan Bicocca, Milan, Italy
  9. 9European Institute of Oncology, Milan, Italy
  10. 10Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  11. 11Klinikum am Gesundbrunnen, SLK-Kliniken Heilbronn GmbH, Heilbronn, Germany
  12. 12Gyncology and Obstetrics, Technische Universitat Dresden Medizinische Fakultat Carl Gustav Carus, Dresden, Germany
  13. 13Obstetrics and Gynecology, Mainz University, Mainz, Germany
  14. 14Gynecology with Center of Oncological Surgery, Charite Universitatsmedizin Berlin, Berlin, Germany
  15. 15Oberschwabenklinik gGmbH, Ravensburg, Baden-Württemberg, Germany
  16. 16University Hospital Cologne, Cologne, Germany
  17. 17Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany
  18. 18AGO Study Group, Wiesbaden, Germany
  1. Correspondence to Dr Florian Heitz, AGO & Ev Kliniken Essen-Mitte, Essen, Germany; florian.heitz{at}gmx.net

Abstract

Background Phase III trial data have shown a significant benefit by the addition of a maintenance treatment with niraparib, irrespective of BRCA or HRD status, in patients with advanced high-grade ovarian cancers; and, a significant benefit of the combination of olaparib and bevacizumab compared with bevacizumab monotherapy in HRD positive patients. However, it is unclear whether a PARP inhibitor monotherapy is sufficient, or if the addition of bevacizumab is needed.

Primary Objectives This trial will investigate if the treatment strategy of carboplatin/paclitaxel/bevacizumab/niraparib is superior to the treatment of carboplatin/paclitaxel/niraparib in an all-comer population.

Study Hypothesis Adding bevacizumab to chemotherapy followed by niraparib maintenance improves progression-free survival in patients with newly diagnosed advanced ovarian cancer.

Trial Design AGO-OVAR 28/ENGOT-ov57 is an international, multicenter, randomized, prospective phase III trial within the the European Network for Gynecological Oncological Trial (ENGOT), led by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) study group. All patients should have completed the first cycle of chemotherapy (carboplatin and paclitaxel) as part of the Study Run-In-Period. Prior to day 1 of cycle 2, patients with a valid central tumor BRCA (tBRCA) test result were randomized in a 1:1 ratio into either: Arm 1, to receive five additional cycles of carboplatin and paclitaxel q21d, followed by niraparib for up to 3 years; or Arm 2, to receive five additional cycles of carboplatin and paclitaxel plus bevacizumab q21d, followed by bevacizumab q21d (for up to 1 year), and niraparib for up to 3 years.

Major Inclusion/Exclusion Criteria The trial population is composed of adult patients with newly diagnosed, advanced high-grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer FIGO III/IV (except FIGO IIIA2 without nodal involvement). Patients who are scheduled for neoadjuvant chemotherapy and interval debulking surgery are also eligible for the trial.

Primary Endpoint The primary endpoint is progression-free survival.

Sample Size The study plans to recruit 970 patients (485 patients in each arm).

Estimated Dates For Completing Accrual And Presenting Results The Last-Patient-In is expected to be enrolled in September 2024, with presentation of the primary endpoint in 2028.

Trial Registration NCT05009082; EudraCT Number: 2021-001271-16

  • Ovarian Cancer

Data availability statement

All data relevant to the study are included in the article.

https://doi.org/10.1136/ijgc-2023-004944

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    Data availability statement

    All data relevant to the study are included in the article.

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    Footnotes

    • Contributors FH is the guarantor and accepts full responsibility for the work or the conduct of the study, had access to the data, and controlled the decision to publish. FH, CM, SH, AR, DC, LG, NC, BS, NDG, PW, AH, JS, MGM, PCS, EH, JH, SP, and PH provided substantial contributions to the conception or design of the work. As the manuscript describes a trial in progress, we anticipate that all authors will be participating in the acquisition, analysis, or interpretation of data for the work. FH, CM, SH, AR, DC, LG, NC, BS, NDG, PW, AH, JS, MGM, PCS, EH, JH, SP, and PH were included in drafting the work or revising it critically for important intellectual content. FH, CM, SH, AR, DC, LG, NC, BS, NDG, PW, AH, JS, MGM, PCS, EH, JH, SP, and PH gave the final approval of the version to be published. FH, CM, SH, AR, DC, LG, NC, BS, NDG, PW, AH, JS, MGM, PCS, EH, JH, SP, and PH gave the agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

    • Funding All support for the present manuscript (eg, funding, provision of study materials, article processing charges, etc.) and the grant for the reported trial is from GSK.

    • Competing interests Grants or contracts from any entity is reported by PH (AstraZeneca, Roche, GSK, Genmab, Immunogen, Seagen, Clovis, and Novartis (all institutional)), by JS (Roche, MSD, GSK, Tesaro, AstraZeneca, MSD, Eisai, Merck, and Novocure), and by NC (Roche, GSK, and AstraZeneca). Consulting fees are reported by FH (NovoCure, PharmaMar, AstraZeneca, Roche, Tesaro, GSK, Clovis, and Amedes), by CM (MSD, Roche, GSK, Seagen, Novartis, and PharmaMar), by LG (GSK, MSD, AstraZeneca, PharmaMar, and Clovis Oncology), by BS (GSK, AstraZeneca, Roche Pharma, MSD, and Eisai), by AH (AstraZeneca, Celgen, GSK, LEO Pharma, MedConcept GmbH, Med update GmbH, Medicultus, Pfizer, Promedicis GmbH, Softconsult, Roche Pharma AG, and Streamedup!GmbH), by PH (AstraZeneca, Roche, GSK, Clovis, Immunogen, MSD, Miltenyi, Novartis, and Eisai), by JS (Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, MSD Eisai, and Merck), and by NC (AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, and Roche). Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events are reported by FH (NovoCure, PharmaMar, AstraZeneca, Roche, Tesaro, GSK, Clovis, and Amedes), by CM (GSK, AstraZeneca, and MSD), by BS (GSK, AstraZeneca, Roche, MSD, and Eisai), by PW (AstraZeneca, Roche, MSD, Eisai, Lilly, GSK, and Daiichi Sankyo), by NDG (Roche, AstraZeneca, Clovis Myriad, Novartis, GSK, and MSD), by PH (Amgen, AstraZeneca, GSK, Roche, Sotio, Stryker, Zai Lab, MSD, Clovis, Eisai, Mersana, and Exscientia), by JS (Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, Bristol Myers Squibb, Eisai, and Novartis), and by NC (AstraZeneca, Novartis, Clovis Oncology, GSK, and MSD/Merck). Participation on a Data Safety Monitoring Board or Advisory Board is reported by CM (GSK and Karypharma), by BS (GSK, AstraZeneca, Roche, MSD, and Eisai), by JS (Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, Bristol Myers Squibb, MSD, Merck, Bayer, and PharmaMar), and by NC (AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, and Roche). Support for attending meetings and/or travel is reported by LG (GSK, MSD, AstraZeneca, and Clovis Oncology) by BS (GSK, AstraZeneca, and Roche) by NDG (AstraZeneca), by PW (Gilead, Novartis, Roche, MSD, AstraZeneca, Lilly, Eisai, Pfizer, GSK, and Daiichi Sankyo), by PH (AstraZeneca), and by JS (GSK, AstraZeneca, Roche, Novocure, Immunogen, Incyte, MSD, and Eisei). Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid is reported by BS (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe), JS (ENGAGE, ESGO, ASCO, ESGO, GCIG, Deutsche Stiftung Eierstockkrebs). AGOJS reports receipt of equipment, materials, drugs, medical writing, gifts, or other services. Medical writing services by MSD. SH reports none; AR reports none; DC reports none; MGM reports none; PCS reports none; EH reports none; SP reports none.

    • Provenance and peer review Not commissioned; internally peer reviewed.