Bradley J Monk1, Andrés Poveda2, Ignace Vergote3, Francesco Raspagliesi4, Keiichi Fujiwara5, Duk-Soo Bae6, Ana Oaknin7, Isabelle Ray-Coquard8, Diane M Provencher9, Beth Y Karlan10, Catherine Lhommé11, Gary Richardson12, Dolores Gallardo Rincón13, Robert L Coleman14, Christian Marth15, Arija Brize16, Michel Fabbro17, Andrés Redondo18, Aristotelis Bamias19, Haijun Ma20, Florian D Vogl21, Bruce A Bach21, Amit M Oza22. 1. Department of Obstetrics and Gynecology, University of Arizona Cancer Center at Dignity Health St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. Electronic address: bradley.monk@chw.edu. 2. Area Clinica de Oncologia Ginecológica, Fundación Instituto Valenciano de Oncología, Valencia, Spain. 3. Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven Cancer Institute, KU Leuven, European Union, Belgium. 4. Gynecologic Oncology Unit, Fondazione IRCCS, Istituto Nazionale per la Cura e lo Studio dei Tumori, Milano, Italy. 5. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka-Shi, Japan. 6. Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, South Korea. 7. Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. 8. Université Lyon-I, Centre Léon Bérard, Lyon, France. 9. Division of Gynecologic Oncology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada. 10. Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 11. Department of Medicine, Institut Gustave Roussy, Villejuif, France. 12. Academic Haematology and Oncology, Cabrini Hospital, Malvern, VIC, Australia. 13. Subdirección de Medicina Interna, Instituto Nacional de Cancerologia, Mexico City, Mexico. 14. Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA. 15. Universitätsklinik für Gynäkologie und Geburtshilfe, Medizinische Universität Innsbruck, Innsbruck, Austria. 16. Latvian Oncology Center, Riga Eastern Clinical University Hospital, Riga, Latvia. 17. Regional Cancer Institute Montpellier, Montpellier, France. 18. Hospital Universitario La Paz Idi-Paz, Madrid, Spain. 19. Alexandra Hospital, Department of Clinical Therapeutics, National & Kapodistrian University of Athens, Athens, Greece. 20. Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, USA. 21. Global Development Oncology, Amgen Inc., Thousand Oaks, CA, USA. 22. Department of Medicine, Princess Margaret Hospital, University of Toronto, ON, Canada.
Abstract
PURPOSE: Trebananib, a peptibody that blocks binding of angiopoietin-1 and -2 to Tie2, significantly prolonged progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer in the phase 3 TRINOVA-1 study. We report overall survival (OS) in the intent-to-treat population and clinically relevant subgroups and time to second disease progression (PFS-2). PATIENTS AND METHODS: Women with recurrent disease (platinum-free interval<12months) were randomized to receive intravenous paclitaxel 80mg/m(2) (3weeks on/1week off) plus intravenous trebananib 15mg/kg or placebo, weekly. OS in the intent-to-treat population was a key secondary endpoint. Exploratory analysis of PFS-2 was conducted according to guidance by the European Medicines Agency. RESULTS:Median OS was not significantly improved with trebananib compared with placebo (19.3 versus 18.3months; HR, 0.95; 95% CI, 0.81-1.11; P=0.52) in the intent-to-treat population (n=919). In subgroup analysis, trebananib improved median OS compared with placebo (14.5 versus 12.3months; HR, 0.72; 95% CI, 0.55-0.93; P=0.011) in patients with ascites at baseline (n=295). In the intent-to-treat population, trebananib significantly improved median PFS-2 compared with placebo (12.5 versus 10.9months; HR, 0.85; 95% CI, 0.74-0.98; P=0.024). The incidence and type of adverse events in this updated analysis was consistent with that described in the primary analysis; no new safety signals were detected. CONCLUSIONS:OS was not significantly longer in the intent-to-treat population, although there was an improvement in OS in patients with ascites receiving trebananib. PFS-2 confirmed that the PFS benefit associated with trebananib was maintained through the second disease progression independent of the choice of subsequent therapy.
RCT Entities:
PURPOSE: Trebananib, a peptibody that blocks binding of angiopoietin-1 and -2 to Tie2, significantly prolonged progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer in the phase 3 TRINOVA-1 study. We report overall survival (OS) in the intent-to-treat population and clinically relevant subgroups and time to second disease progression (PFS-2). PATIENTS AND METHODS: Women with recurrent disease (platinum-free interval<12months) were randomized to receive intravenous paclitaxel 80mg/m(2) (3weeks on/1week off) plus intravenous trebananib 15mg/kg or placebo, weekly. OS in the intent-to-treat population was a key secondary endpoint. Exploratory analysis of PFS-2 was conducted according to guidance by the European Medicines Agency. RESULTS: Median OS was not significantly improved with trebananib compared with placebo (19.3 versus 18.3months; HR, 0.95; 95% CI, 0.81-1.11; P=0.52) in the intent-to-treat population (n=919). In subgroup analysis, trebananib improved median OS compared with placebo (14.5 versus 12.3months; HR, 0.72; 95% CI, 0.55-0.93; P=0.011) in patients with ascites at baseline (n=295). In the intent-to-treat population, trebananib significantly improved median PFS-2 compared with placebo (12.5 versus 10.9months; HR, 0.85; 95% CI, 0.74-0.98; P=0.024). The incidence and type of adverse events in this updated analysis was consistent with that described in the primary analysis; no new safety signals were detected. CONCLUSIONS: OS was not significantly longer in the intent-to-treat population, although there was an improvement in OS in patients with ascites receiving trebananib. PFS-2 confirmed that the PFS benefit associated with trebananib was maintained through the second disease progression independent of the choice of subsequent therapy.
Authors: Sarah E S Leary; Julie R Park; Joel M Reid; Andrew T Ralya; Sylvain Baruchel; Bing Wu; Timothy P L Roberts; Xiaowei Liu; Charles G Minard; Elizabeth Fox; Brenda Weigel; Susan Blaney Journal: Clin Cancer Res Date: 2017-07-27 Impact factor: 12.531
Authors: Elizabeth A Kuczynski; Peter B Vermeulen; Francesco Pezzella; Robert S Kerbel; Andrew R Reynolds Journal: Nat Rev Clin Oncol Date: 2019-08 Impact factor: 66.675