TY - JOUR
T1 - 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)
AU - Harter, Philipp
AU - Pautier, Patricia
AU - Van Nieuwenhuysen, Els
AU - Reuss, Alexander
AU - Redondo, Andres
AU - Lindemann, Kristina
AU - Kurzeder, Christian
AU - Petru, Edgar
AU - Heitz, Florian
AU - Sehouli, Jalid
AU - Degregorio, Nikolaus
AU - Wimberger, Pauline
AU - Burges, Alexander
AU - Cron, Nadin
AU - Ledermann, Jonathan
AU - Lorusso, Domenica
AU - Paoletti, Xavier
AU - Marme, Frederik
N1 - Funding Information:
1Gynecology and Gynecologic Oncology, AGO & Ev. Kliniken Essen-Mitte, Essen, Germany 2GINECO & Gustave Roussy, Villejuif, France 3Gynecological Oncology, BGOG & University Hospitals Leuven, Leuven, Belgium 4Coordinating Centre for Clinical Trials, AGO & Philipps-University, Marburg, Germany 5IdiPaz, GEICO & Hospital Universitario La Paz, Madrid, Spain 6NSGO & Oslo University Hospital, Unversity of Oslo, Oslo, Norway 7SAKK & University Hospital of Basel, Basel, Switzerland 8AGO-Austria & Graz University, Graz, Austria 9Department of Gynecology with Center for Oncological Surgery, Campus Virchow Klinikum, AGO & Charité Berlin, Berlin, Germany 10AGO & University Ulm, Ulm, Germany 11Gyncology and Obstetrics, AGO & TU Dresden, Dresden, Germany 12AGO & LMU Munich, Munchen, Bayern, Germany 13AGO, Essen, Germany 14UCL Cancer Institute, University College, London, UK 15Policlinico Gemelli, Rome, Italy 16Institute Curie, Paris, France 17AGO & University Mannheim, Mannheim, Germany Acknowledgements We would like to thank the participating study groups: Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Studiengruppe, AGO Austria, Belgian Gynecologic Oncology Group (BGOG), Grupo Espagnol de Investigation en Cancer de Ovario (GEICO), Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Nordic Society of Gynecologic Oncology (NSGO), and Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK). In addition, we would like to thank F. Hoffmann-La Roche Ltd for financial support and providing the study drugs. Furthermore, we would like to thank Iqbal Hügel and his team from SPS for monitoring services.
Funding Information:
This study was funded by F. Hoffmann-La Roche.
Funding Information:
Competing interests PH reports grants and personal fees from Astra Zeneca, grants and personal fees from Roche, personal fees from Sotio, grants and personal fees from Tesaro, personal fees from Stryker, personal fees from Zai Lab, personal fees from MSD, grants and personal fees from public funding (ASCO, DKH, DFG), personal fees from Clovis, personal fees from Immunogen, grants from GSK, grants from Boehringer Ingelheim, grants from Medac, grants from Genmab, outside the submitted work. PP reports personal fees from Roche Laboratory, other personal fees from MSD laboratory, other from Clovis Oncology, outside the submitted work. AR reports grants and personal fees from Pharmamar, personal fees from Lilly, personal fees from Novartis, personal fees from Amgen, personal fees from Astra Zeneca, personal fees from Tesaro, grants and personal fees from Roche, grants from Eisai, outside the submitted work. KL reports other personal fees from Astra Zeneca, other from GSK, outside the submitted work. CK reports personal fees and non-financial support from Roche, personal fees and non-financial support from Tessaro, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Pharmamar, personal fees from Lilly, personal fees from Genomic Health, outside the submitted work. EP reports personal fees from AGEA, personal fees from Amgen, personal fees from Astra Zeneca, personal fees from Angelini, personal fees from Celgene, personal fees from Eisai, personal fees from Eli Lilly, personal fees from GSK, personal fees from MSD, personal fees from Novartis, personal fees from Pharmamar, personal fees from Pfizer, personal fees from Roche, personal fees from Tesaro, personal fees from Clovis, personal fees from Daiichi Sankyo, outside the submitted work. FH reports non-financial support from NewOncology; personal fees from Roche, personal fees from AstraZeneca, from Clovis, personal fees from Tesaro, from PharmaMar, outside the submitted work. JS reports grants, non-financial support and other from Roche, grants, nonfinancial support, and other perdonal fees from PharmaMar, grants, non-financial support and other peredonal fees from Teasaro, grants, non-financial support and other personal fees from Clovis, grants, non-financial support and other peersonal fees from Astra Zeneca, grants and non-financial support from MSD, grants, nonfinancial support and other personal fees from Novocure, outside the submitted work. ND: Dr. de Gregorio reports personal fees from Roche, personal fees from GSK, personal fees from Pharmamar, personal fees from Astra Zeneca, personal fees from Clovis, personal fees from Ingress, from null, outside the submitted work. PW reports grants and personal fees from Amgen, personal fees from Astra Zeneca, personal fees from Clovis, personal fees from MSD, grants and personal fees from Novartis, personal fees from Pfizer, grants and personal fees from Roche, personal fees from Tesaro, personal fees from Eisai, personal fees from Pharmamar, personal fees from Teva, outside the submitted work. JL reports personal fees and other from Pfizer, grants and other from Merck/MSD, personal fees from Eisai, personal fees from Tesaro/GSK, grants and personal fees from AstraZeneca, personal fees from Artios, personal fees from Regeneron, outside the submitted work. DL reports grants, personal fees and non-financial support from Roche, grants, personal fees and non-financial support from Tesaro, grants and personal fees from Clovis, grants and personal fees from Merck, grants, personal fees and non-financial support from Pharmamar, personal fees from Immunogen, personal fees from Genmab, personal fees from Amgen, personal fees and non-financial support from Astra Zeneca, outside the submitted work. FM reports personal fees from Roche, personal fees from AstraZeneca, personal fees from Pfizer, personal fees from Tesaro, personal fees from Novartis, personal fees from Amgen, personal fees from PharmaMar, personal fees from GenomicHealth, personal fees from CureVac, personal fees from EISAI, outside the submitted work.
Publisher Copyright:
©
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
KW - ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=85088402870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088402870&partnerID=8YFLogxK
U2 - 10.1136/ijgc-2020-001572
DO - 10.1136/ijgc-2020-001572
M3 - Article
C2 - 32606097
AN - SCOPUS:85088402870
VL - 30
SP - 1997
EP - 2001
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
SN - 1048-891X
IS - 12
ER -