Clinical trialPhase 3Ovarian cancer

Bevacizumab Combined With Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial

JCO · 2014361 patients

Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. JCO. 2014. 32:1302-1308

Study type: Clinical trial
Study name: AURELIA
Phase: Phase 3
Design: Randomised, open-label trial
Sample size: 361 patients
Source: JCO · 2014

In plain words

In patients whose ovarian cancer had grown again less than 6 months after finishing treatment with platinum drugs, adding the medicine bevacizumab to chemotherapy roughly doubled the time the disease was kept under control without getting worse (median 6.7 months versus 3.4 months). The tumour shrank in a larger share of patients. The effect of this combination on overall length of life was not statistically significant. Side effects such as high blood pressure and protein in the urine were more common with bevacizumab, and a hole in the bowel occurred in 2.2% of patients.

Key results

0.48 (95% CI 0.38 to 0.60)

Progression-free survival (HR)

P<0.001; 301 events in 361 patients

6.7 months with bevacizumab vs 3.4 months with chemotherapy alone

Median progression-free survival

27.3% vs 11.8%

Objective response rate (RECIST)

P=0.001

0.85 (95% CI 0.66 to 1.08)

Overall survival (HR)

P=0.174; not significant

16.6 months vs 13.3 months

Median overall survival

Bevacizumab versus chemotherapy alone

Drugs in this study:Bevacizumab (Avastin)Doxorubicin (Adriamycin)Paclitaxel (Taxol)

Dose and schedule cards

Single-agent chemotherapy + bevacizumab (AURELIA)

Platinum-resistant recurrence (less than 6 months after the last platinum), no more than 2 prior regimens; in the trial, rectosigmoid or bowel involvement and symptoms of bowel obstruction were exclusion criteriaOn the page “Ovarian cancer” · Platinum-resistant recurrence

Drug	Dose	Route	Schedule
One of the three
Paclitaxel	80 mg/m²	IV	Days 1, 8, 15 and 22 every 4 weeks
Pegylated liposomal doxorubicin (PLD)	40 mg/m²	IV	Day 1 every 4 weeks
Topotecan	4 mg/m² (days 1, 8 and 15 every 4 weeks) or 1.25 mg/m² (days 1 to 5 every 3 weeks)	IV	As scheduled
Concurrent
Bevacizumab	10 mg/kg every 2 weeks (with paclitaxel, PLD or weekly topotecan) or 15 mg/kg every 3 weeks (with topotecan every 3 weeks)	IV	Day 1

Cycle length: 28 days (or 21 days for topotecan days 1 to 5)
Duration: Until progression or unacceptable toxicity

Chemotherapy doses are from the AURELIA (MO22224) regimen in the bevacizumab label; the single-agent label doses differ: PLD 50 mg/m² every 4 weeks and topotecan 1.5 mg/m² days 1 to 5 every 21 days. PLD: assess left ventricular function before starting (risk of cardiomyopathy with cumulative anthracycline dose). ESMO: early palliative care.

On the page “Ovarian cancer” · Platinum-resistant recurrence

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Single-agent chemotherapy alone

Chemotherapy of investigator's choice: paclitaxel 80 mg/m² IV on days 1, 8, 15 and 22 every 4 weeks; or pegylated liposomal doxorubicin 40 mg/m² IV on day 1 every 4 weeks; or topotecan 4 mg/m² IV on days 1, 8 and 15 every 4 weeks or 1.25 mg/m² on days 1 to 5 every 3 weeks. Continued until progression, unacceptable toxicity or withdrawal; after progression, crossover to single-agent bevacizumab was allowed (40% of patients).

2Chemotherapy with bevacizumab

The same chemotherapy plus bevacizumab 10 mg/kg IV every 2 weeks (with weekly paclitaxel, liposomal doxorubicin or weekly topotecan) or 15 mg/kg every 3 weeks (with topotecan on days 1 to 5 every 3 weeks), until progression or unacceptable toxicity.

Source of the regimen details: FDA label for Avastin (DailyMed, section 14.8, study MO22224 = AURELIA) and abstract of the paper

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with epithelial ovarian, fallopian tube or primary peritoneal cancer with measurable or assessable disease that had progressed less than 6 months after completing platinum-based therapy (platinum-resistant), with no more than 2 prior chemotherapy regimens. Primary refractory disease, a history of bowel obstruction, rectosigmoid involvement on pelvic examination or bowel involvement on CT, and clinical symptoms of bowel obstruction were exclusion criteria.

Endpoints

Primary endpoint: progression-free survival (PFS) by RECIST. Secondary endpoints: objective response rate (ORR), overall survival (OS), safety and patient-reported outcomes.

Safety and side effects

Grade 2 or higher hypertension and proteinuria were more frequent in the bevacizumab group. Gastrointestinal perforation occurred in 2.2% of bevacizumab-treated patients. No new safety signals were observed.

Clinical significance and place in guidelines

This trial showed that adding bevacizumab to single-agent chemotherapy in platinum-resistant ovarian cancer improves PFS and ORR, although the improvement in overall survival was not statistically significant. According to the abstract, no new safety signals were seen. The status of drug approvals and clinical guideline recommendations should be checked separately and is not mentioned in the abstract.

Limitations

The trial design was open-label. Overall survival, a secondary endpoint, showed no significant difference. Crossover of patients in the chemotherapy-alone group to bevacizumab after disease progression was allowed. Patients with refractory disease, a history of bowel obstruction or more than two prior regimens were excluded.

Original article (DOI)PubMed

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.