Eric Pujade-Lauraine1, Felix Hilpert, Béatrice Weber, Alexander Reuss, Andres Poveda, Gunnar Kristensen, Roberto Sorio, Ignace Vergote, Petronella Witteveen, Aristotelis Bamias, Deolinda Pereira, Pauline Wimberger, Ana Oaknin, Mansoor Raza Mirza, Philippe Follana, David Bollag, Isabelle Ray-Coquard. 1. Eric Pujade-Lauraine, Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris; Béatrice Weber, GINECO and Centre Alexis Vautrin, Vandoeuvre-les-Nancy; Philippe Follana, GINECO and Centre Antoine-Lacassagne, Nice; Isabelle Ray-Coquard, GINECO and Centre Léon Bérard, Lyon, France; Felix Hilpert, Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Klinik für Gynäkologie und Geburtshilfe, Kiel; Alexander Reuss, AGO and Coordinating Center for Clinical Trials, Marburg; Pauline Wimberger, AGO and University of Duisburg-Essen, Essen, Germany; Andres Poveda, Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Instituto Valenciano de Oncologia, Valencia; Ana Oaknin, GEICO and Vall d'Hebron University Hospital, Barcelona, Spain; Gunnar Kristensen, Nordic Society of Gynaecological Oncology (NSGO) and Norwegian Radium Hospital, Oslo, Norway; Roberto Sorio, Multicenter Italian Trials in Ovarian Cancer and Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy; Ignace Vergote, Belgian Gynaecological Oncology Group and University Hospital Leuven, Leuven, Belgium; Petronella Witteveen, Dutch Gynecological Oncology Group and University Medical Center Utrecht, Utrecht, the Netherlands; Aristotelis Bamias, Hellenic Cooperative Oncology Group and University of Athens, Athens, Greece; Deolinda Pereira, GINECO and Instituto Português de Oncologia do Porto, Porto, Portugal; Mansoor Raza Mirza, NSGO and Rigshospitalet, Copenhagen, Denmark; and David Bollag, F. Hoffmann-La Roche, Basel, Switzerland.
Abstract
PURPOSE: In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC. PATIENTS AND METHODS: Eligible patients had measurable/assessable OC that had progressed < 6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or > two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. RESULTS: The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients. CONCLUSION: Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.
RCT Entities:
PURPOSE: In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC. PATIENTS AND METHODS: Eligible patients had measurable/assessable OC that had progressed < 6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or > two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. RESULTS: The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients. CONCLUSION: Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.
Authors: Nicole D Fleming; Robert L Coleman; Celestine Tung; Shannon N Westin; Wei Hu; Yunjie Sun; Priya Bhosale; Mark F Munsell; Anil K Sood Journal: Gynecol Oncol Date: 2017-08-01 Impact factor: 5.482
Authors: José Baselga; Nina Bhardwaj; Lewis C Cantley; Ronald DeMatteo; Raymond N DuBois; Margaret Foti; Susan M Gapstur; William C Hahn; Lee J Helman; Roy A Jensen; Electra D Paskett; Theodore S Lawrence; Stuart G Lutzker; Eva Szabo Journal: Clin Cancer Res Date: 2015-10-01 Impact factor: 12.531
Authors: Sara M Federico; Kenneth J Caldwell; Mary B McCarville; Vinay M Daryani; Clinton F Stewart; Shenghua Mao; Jianrong Wu; Andrew M Davidoff; Victor M Santana; Wayne L Furman; Alberto S Pappo; Fariba Navid Journal: Eur J Cancer Date: 2020-04-20 Impact factor: 9.162
Authors: Carol Aghajanian; Barbara Goff; Lawrence R Nycum; Yan V Wang; Amreen Husain; Stephanie V Blank Journal: Gynecol Oncol Date: 2015-08-10 Impact factor: 5.482