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2022-RA-1725-ESGO Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer- results of a multicentre NOGGO phase I and II study (TOPAZ)
  1. Tjadina Arndt1,
  2. Radoslav Chekerov1,
  3. Klaus Pietzner1,
  4. Isil Yalcinkaya1,
  5. Ulrich Canzler2,
  6. Pauline Wimberger2,
  7. Hans Georg Strauß3,
  8. Sven Mahner4,
  9. Linn Woelber5,
  10. Nikolaus de Gregorio6,
  11. Ulrich Thorsten Hacker7,
  12. Ekkehard von Abel8,
  13. Rolf Richter1 and
  14. Jalid Sehouli1
  1. 1Gynecology, Competence Center for Ovarian Cancer (EKZE), Charité, Charite, Universitätsklinikum Berlin, Germany
  2. 2Department of Gynecology and Obstetrics, TU Dresden Medizinische Fakultat Carl Gustav Carus, Dresden, Dresden, Germany
  3. 3Department of Gynaecology, University of Halle, Klinikum Ludwigshafen, Halle, Germany
  4. 4Obstetrics and Gynaecology, University Hospital, Ludwig-Maximilian-University, Munich, Munich, Germany
  5. 5Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  6. 6Department of Obstetrics and Gynaecology, University of Ulm, SLK Kliniken Heilbronn, Ulm, Germany
  7. 7Clinic and Polyclinic for Oncology, Gastroenterology, Hepatology, Pneumology and Infectiology, University Cancer Center Leipzig, university leipzig, leipzig, Germany
  8. 8Department of Gynecology and Obstetrics, Stauferklinikum Schwäbisch Gmünd, Schwäbisch Gmünd, Germany


Introduction/Background Patients with recurrent ovarian cancer (ROC) have a particularly poor prognosis. So far recurrent treatment are mostly restricted by previous toxicity and of limited activity. The role of adding modern multi-targeted tyrosine kinase inhibitors (TKIs) for targeting angiogenesis could be a proimising therapeutic strategy. The investigator-initiated multicentre TOPAZ trial aimed to evaluate the safety and efficacy of the combination of Topotecan with Pazopanib.

Methodology Patients with platinum-resistant ROC with no more than two prior lines of chemotherapy were enrolled. The chemotherapy backbone was based on weekly Topotecan (4 mg/m2, d1,8,15 q28d). In phase I, pazopanib was added orally 400 mg/d in a dose-escalating regime to determine the maximum tolerated dose (MTD). The aim of phase II was to evaluate the safety and efficacy of pazopanib in the optimal MTD together with weekly Topotecan based on progression-free survival.

Results From June 2012 to February 2017, 11 patients were enrolled in phase I and 50 patients in phase II. The MTD of pazopanib was set at 400 mg/d. In phase I, the most common adverse event was haematological toxicity. In phase II, the median progression-free survival was 3,5 months (95% CI:2.0–5.0 months), with haematological toxicity being the most common reason for dose change and treatment delays. The combination of Topotecan and Pazopanib is shown to be feasibble in terms of safety profile. It offers no clinical advantage in progression-free or overall survival compared to Topotecan monotherapy.

Conclusion Adding pazopanib to topotecan is safe and feasible, but does not seem to have any clinical benefit. We will not pursue this combination. Further studies are needed that pursue the approach of novel combination therapies with chemotherapy and anti-angiogenesis inhibitors. In addition, the promising therapeutic options with PARP and immune checkpoint inhibitors should also be considered.

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