Christian Marth1, Ignace Vergote2, Giovanni Scambia3, Willi Oberaigner4, Andrew Clamp5, Regina Berger6, Christian Kurzeder7, Nicoletta Colombo8, Peter Vuylsteke9, Domenica Lorusso10, Marcia Hall11, Vincent Renard12, Sandro Pignata13, Rebecca Kristeleit14, Sevilay Altintas15, Gordon Rustin11, Robert M Wenham16, Mansoor Raza Mirza17, Peter C Fong18, Amit Oza19, Bradley J Monk20, Haijun Ma21, Florian D Vogl21, Bruce A Bach21. 1. AGO-Austria and Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: Christian.MARTH@tirol-kliniken.at. 2. BGOG and Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven Cancer Institute, KU Leuven, Belgium. 3. MITO and Dipartimento per la Tutela della Salute della Donna e della Vita Nascente del Bambino e Adolescente, Policlinico Universitario Agostino Gemelli, Roma, Italy. 4. AGO-Austria and Department of Clinical Epidemiology of the Tirol Kliniken Ltd., Cancer Registry of Tyrol, Innsbruck, Austria. 5. Department of Medical Oncology, Institute of Cancer Sciences, University of Manchester, The Christie NHS Foundation Trust, Manchester, UK. 6. AGO-Austria and Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria. 7. AGO-Study Group and Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany. 8. MANGO and Istituto Europeo di Oncologia and Università Milano Bicocca, Milano, Italy. 9. BGOG and Department of Medical Oncology, CHU Université Catholique de Louvain, Site Sainte Elisabeth, Namur, Belgium. 10. MITO and Unità di Ginecologia Oncologica, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy. 11. Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK. 12. BGOG and Department of Oncology, AZ St. Lucas, Ghent, Belgium. 13. MITO and Department of Urology and Gynecology, Istituto Nazionale Tumori "Fondazione G. Pascale" IRCCS, Naples, Italy. 14. Department of Medical Oncology, University College London Cancer Institute, London, UK. 15. BGOG and Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium. 16. Department of Gynecologic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 17. NSGO & Department of Oncology, Rigshospitalet, København, Denmark. 18. Medical Oncology Department, Auckland City Hospital, Auckland, New Zealand. 19. Department of Medicine, Princess Margaret Hospital, University of Toronto, ON, Canada. 20. Department of Obstetrics and Gynecology, University of Arizona Cancer Center at Dignity Health St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. 21. Global Development Oncology, Amgen Inc., Thousand Oaks, CA, USA.
Abstract
AIMS: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. METHODS:Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m2 once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo. PFS was the primary end-point; key secondary end-points were objective response rate (ORR) and duration of response (DOR). Owing to PLD shortages, enrolment was paused for 13 months; the study was subsequently truncated. RESULTS:Two hundred twenty-three patients were enrolled. Median PFS was 7.6 months (95% CI, 7.2-9.0) in the trebananib arm and 7.2 months (95% CI, 4.8-8.2) in the placebo arm, with a hazard ratio of 0.92 (95% CI, 0.68-1.24). However, because the proportional hazards assumption was not fulfilled, the standard Cox model did not provide a reliable estimate of the hazard ratio. ORR in the trebananib arm was 46% versus 21% in the placebo arm (odds ratio, 3.43; 95% CI, 1.78-6.64). Median DOR was improved (trebananib, 7.4 months [95% CI, 5.7-7.6]; placebo, 3.9 months [95% CI, 2.3-6.5]). Adverse events with a greater incidence in the trebananib arm included localised oedema (61% versus 32%), ascites (29% versus 9%) and vomiting (45% versus 33%). CONCLUSIONS:Trebananib demonstrated anticancer activity in this phase 3 study, indicated by improved ORR and DOR. Median PFS was not improved. No new safety signals were identified. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01281254.
RCT Entities:
AIMS: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. METHODS:Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m2 once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo. PFS was the primary end-point; key secondary end-points were objective response rate (ORR) and duration of response (DOR). Owing to PLD shortages, enrolment was paused for 13 months; the study was subsequently truncated. RESULTS: Two hundred twenty-three patients were enrolled. Median PFS was 7.6 months (95% CI, 7.2-9.0) in the trebananib arm and 7.2 months (95% CI, 4.8-8.2) in the placebo arm, with a hazard ratio of 0.92 (95% CI, 0.68-1.24). However, because the proportional hazards assumption was not fulfilled, the standard Cox model did not provide a reliable estimate of the hazard ratio. ORR in the trebananib arm was 46% versus 21% in the placebo arm (odds ratio, 3.43; 95% CI, 1.78-6.64). Median DOR was improved (trebananib, 7.4 months [95% CI, 5.7-7.6]; placebo, 3.9 months [95% CI, 2.3-6.5]). Adverse events with a greater incidence in the trebananib arm included localised oedema (61% versus 32%), ascites (29% versus 9%) and vomiting (45% versus 33%). CONCLUSIONS: Trebananib demonstrated anticancer activity in this phase 3 study, indicated by improved ORR and DOR. Median PFS was not improved. No new safety signals were identified. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01281254.
Authors: Bhavana Pothuri; Allison L Brodsky; Joseph A Sparano; Stephanie V Blank; Mimi Kim; Dawn L Hershman; Amy Tiersten; Brian F Kiesel; Jan H Beumer; Leonard Liebes; Franco Muggia Journal: Cancer Chemother Pharmacol Date: 2020-02-13 Impact factor: 3.333
Authors: Grégory Thiabaud; Guangan He; Sajal Sen; Kathryn A Shelton; Wallace B Baze; Luke Segura; Julie Alaniz; Ruben Munoz Macias; Greg Lyness; Alan B Watts; Hyun Min Kim; Hyunseung Lee; Mi Young Cho; Kwan Soo Hong; Rick Finch; Zahid H Siddik; Jonathan F Arambula; Jonathan L Sessler Journal: Proc Natl Acad Sci U S A Date: 2020-03-16 Impact factor: 11.205