Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.

TitleBevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.
Publication TypeJournal Article
Year of Publication2014
AuthorsPujade-Lauraine, E, Hilpert, F, Weber, B, Reuss, A, Poveda, AM, Kristensen, GB, Sorio, R, Vergote, IB, Witteveen, P, Bamias, A, Pereira, D, Wimberger, P, Oaknin, A, Mirza, MRaza, Follana, P, Bollag, D, Ray-Coquard, I
JournalJ Clin Oncol
Volume32
Start Page1302
Issue13
Pagination1308
Date Published05/2014
ISSN1527-7755
KeywordsAdult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Disease-Free Survival, Doxorubicin, Drug Administration Schedule, Drug Resistance, Neoplasm, Female, Humans, Middle Aged, Neoplasm Recurrence, Local, Organoplatinum Compounds, Ovarian Neoplasms, Paclitaxel, Polyethylene Glycols, Topotecan
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.

DOI10.1200/JCO.2013.51.4489
Alternate JournalJ. Clin. Oncol.
PubMed ID24637997