AURELIA: A Multi-center, Open-label, Randomised, Two-arm Phase III Trial of the Effect on Progression Free Survival of Bevacizumab Plus Chemotherapy Versus Chemotherapy Alone in Patients With Platinum-resistant, Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer

Trial ID # NCT00976911; AURELIA
Phase III
Drug Class Angiogenesis Inhibitors: VEGF
Drug Name Bevacizumab
Alternate Drug Names immunoglobulin G1 (human-mouse monoclonal rhuMab-VEGF gamma-chain, anti-VEGF monoclonal antibody, Avastin
Drugs in Trial Bevacizumab, Liposomal doxorubicin, Paclitaxel, Topotecan
Eligible Participant

Platinum-resistant, ≤ 2 prior therapies

Patients Enrolled

361

Therapy Setting

Recurrence

Study Design

Open-Label, Randomized

Endpoints

ORR, PFS, OS, evaluated per RECIST

Efficacy

Pac/PLD/Top+Bev vs Pac/PLD/Top:

ORR: 28.2 vs 12.5% (p=0.001)
PFS: 6.7 vs 3.4 months, HR: 0.46 (0.37-0.58, p<0.0001)
OS: 16.6 vs 13.3 months, HR: 0.83 (0.66–1.06; p=0.14)

Exploratory analysis Pac/PLD/Top:
Pac (weekly, on day 1, 8, 15, 22 of every 4 weeks) (n=115):
ORR: 53.3 vs 30.2%, PFS: 10.4 vs 3.9 months, HR: 0.46 (0.30-0.71); OS: 22.4 vs 13.2 months, HR: 0.65 (0.42-1.02)
PLD (day 1 every four weeks) (n=126):
ORR: 13.7 vs 7.8%, PFS: 5.4 vs 3.5 months, HR: 0.57 (0.39–0.83); OS: 13.7 vs 14.1 months, HR: 0.91 (0.62-1.36)
Top (weekly, on days 1, 8, 15 every four weeks or days 1-5 every 3 weeks) (n=120):
ORR: 17.0 vs 0.0%, PFS: 5.8 vs 2.1 months, HR: 0.32 (0.21-0.49); OS: 13.8 vs 13.3 months, HR: 1.09 (0.72-1.67)

Clinically Significant Adverse Events

Pac/PLD/Top+Bev vs Pac/PLD/Top:
Serious AE: GI perforation (1.7% vs 1 pt), fistula/abscess (2.2% vs 0), arterial thromboembolic event (1.7% vs 1 pt)
Grade 2-4 AE: GI perforation (2.2% vs 0), hypertension (20 vs 7%)

Conclusion

Improved ORR and PFS with addition of Bevacizumab (most evident with Paclitaxel); No OS benefit

Reference

Pujade-Lauraine E et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol (2014) 32(13):1302-
http://www.ncbi.nlm.nih.gov/pubmed/24637997

Poveda AM et al. Bevacizumab Combined With Weekly Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan in Platinum-Resistant Recurrent Ovarian Cancer: Analysis by Chemotherapy Cohort of the Randomized Phase III AURELIA Trial. J Clin Oncol (2015) 33(32): 3836-8
http://www.ncbi.nlm.nih.gov/pubmed/26282651