Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer - a randomized phase III trial (AGO-OVAR 2.29/ENGOT-ov34).
- Harter P Gynecology and Gynecologic Oncology, AGO & Ev. Kliniken Essen-Mitte, Essen, Germany p.harter@gmx.de.
- Pautier P GINECO & Gustave Roussy, Villejuif, France.
- Van Nieuwenhuysen E Gynecological Oncology, BGOG & University Hospitals Leuven, Leuven, Belgium.
- Reuss A Coordinating Centre for Clinical Trials, AGO & Philipps-University, Marburg, Germany.
- Redondo A IdiPaz, GEICO & Hospital Universitario La Paz, Madrid, Spain.
- Lindemann K NSGO & Oslo University Hospital, Unversity of Oslo, Oslo, Norway.
- Kurzeder C SAKK & University Hospital of Basel, Basel, Switzerland.
- Petru E AGO-Austria & Graz University, Graz, Austria.
- Heitz F Gynecology and Gynecologic Oncology, AGO & Ev. Kliniken Essen-Mitte, Essen, Germany.
- Sehouli J Department of Gynecology with Center for Oncological Surgery, Campus Virchow Klinikum, AGO & Charité Berlin, Berlin, Germany.
- Degregorio N AGO & University Ulm, Ulm, Germany.
- Wimberger P Gyncology and Obstetrics, AGO & TU Dresden, Dresden, Germany.
- Burges A AGO & LMU Munich, Munchen, Bayern, Germany.
- Cron N AGO, Essen, Germany.
- Ledermann J UCL Cancer Institute, University College, London, UK.
- Lorusso D Policlinico Gemelli, Rome, Italy.
- Paoletti X Institute Curie, Paris, France.
- Marme F AGO & University Mannheim, Mannheim, Germany.
- 2020-07-02
Published in:
- International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. - 2020
English
BACKGROUND
Improvement in clinical outcomes of patients with platinum-resistant disease is an unmet medical need and trials in this population are urgently needed. Checkpoint-inhibitors have already shown activity in multiple other tumor entities and ovarian cancer, especially in the combination with anti-angiogenic treatment.
PRIMARY OBJECTIVE
To test if the activity of non-platinum-based chemotherapy and bevacizumab could be improved by the addition of atezolizumab.
STUDY HYPOTHESIS
The addition of atezolizumab to standard non-platinum combination of chemotherapy and bevacizumab improves median overall survival from 15 to 20 months.
TRIAL DESIGN
Patients are randomized to chemotherapy (paclitaxel weekly or pegylated liposomal doxorubicin) + bevacizumab + placebo vs chemotherapy + bevacizumab + atezolizumab. Stratification factors are: number of prior lines, planned type of chemotherapy, prior use of bevacizumab, and tumor programmed death-ligand 1 (PD-L1) status.
MAJOR INCLUSION/EXCLUSION CRITERIA
Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with up to three prior therapies and a treatment-free interval after platinum of less than 6 months. Patients with three prior lines of chemotherapy are eligible irrespective of the platinum free-interval. A de novo tumor tissue sample biopsy for determination of PD-L1 status prior to randomization for stratification is mandatory. Major exclusion criteria consider bevacizumab-specific and immunotherapy-specific criteria.
PRIMARY ENDPOINT
Overall survival and progression-free survival are co-primary endpoints.
SAMPLE SIZE
It is planned to randomize 664 patients.
TRIAL REGISTRATION
NCT03353831.
Improvement in clinical outcomes of patients with platinum-resistant disease is an unmet medical need and trials in this population are urgently needed. Checkpoint-inhibitors have already shown activity in multiple other tumor entities and ovarian cancer, especially in the combination with anti-angiogenic treatment.
PRIMARY OBJECTIVE
To test if the activity of non-platinum-based chemotherapy and bevacizumab could be improved by the addition of atezolizumab.
STUDY HYPOTHESIS
The addition of atezolizumab to standard non-platinum combination of chemotherapy and bevacizumab improves median overall survival from 15 to 20 months.
TRIAL DESIGN
Patients are randomized to chemotherapy (paclitaxel weekly or pegylated liposomal doxorubicin) + bevacizumab + placebo vs chemotherapy + bevacizumab + atezolizumab. Stratification factors are: number of prior lines, planned type of chemotherapy, prior use of bevacizumab, and tumor programmed death-ligand 1 (PD-L1) status.
MAJOR INCLUSION/EXCLUSION CRITERIA
Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with up to three prior therapies and a treatment-free interval after platinum of less than 6 months. Patients with three prior lines of chemotherapy are eligible irrespective of the platinum free-interval. A de novo tumor tissue sample biopsy for determination of PD-L1 status prior to randomization for stratification is mandatory. Major exclusion criteria consider bevacizumab-specific and immunotherapy-specific criteria.
PRIMARY ENDPOINT
Overall survival and progression-free survival are co-primary endpoints.
SAMPLE SIZE
It is planned to randomize 664 patients.
TRIAL REGISTRATION
NCT03353831.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1136/ijgc-2020-001572
- PMID 32606097
- Persistent URL
- https://sonar.ch/global/documents/92572
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