The evidence supporting this protocol is provided by a phase III multicentre international randomised trial (AURELIA) involving 361 patients comparing bevacizumab and investigator’s choice chemotherapy (paclitaxel, pegylated liposomal doxorubicin [PLD] or topotecan) (BEV+CT arm) with investigator’s choice chemotherapy alone (CT arm) in patients with recurrent, platinum-resistant ovarian cancer.r
Between October 2009 and April 2011, 179 patients were randomised to receive bevacizumab (10 mg/kg every 2 weeks for patients receiving paclitaxel, PLD or 4-weekly topotecan regimen; or 15 mg/kg every 3 weeks for patients receiving 3-weekly topotecan) with investigator’s choice chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, 15, and 22 every 4 weeks; PLD 40 mg/m2 on day 1 every 4 weeks; or topotecan 4 mg/m2 on days 1, 8, and 15 every 4 weeks or 1.25 mg/m2 on days 1 to 5 every 3 weeks) and 182 patients were randomised to receive investigator’s choice chemotherapy alone. Crossover to single-agent bevacizumab was allowed after progression with chemotherapy alone at the discretion of the investigators.r
Investigator choice of chemotherapy was evenly distributed among the 3 options due to capping of the cohorts (PLD n=126, paclitaxel n=115, topotecan n=120).r
The primary end point was progression-free survival (PFS) and secondary end points were objective response rate (ORR), overall survival (OS), safety, tolerability and quality of life.r
Efficacy
After a median follow up of 13.9 months in the BEV-CT arm and 13 months in the CT arm, the PFS was 3.4 months (95% CI 2.2 to 3.7) in the CT arm compared to 6.7 months (95% CI 5.7 to 7.9) in the BEV+CT arm (HR=0.48, 95% CI 0.38 to 0.60, p<0.001).r
ORR evaluable by RECIST and/or GCIG CA-125 criteria was 12.6% versus 30.9% in CT and BEV+CT arms, respectively (95% CI 9.6 to 27.0, p<0.001). There was no statistically significant improvement in OS in the experimental arm (HR=0.85, 95% CI 0.66 to 1.08, p<0.174). Median OS was 13.3 months (95% CI 11.9 to 16.4) in the CT group versus 16.6 months (95% CI 13.7 to 19.0) in BEV+CT group.r
Kaplan-Meier curve of progression-free survivalr
© J Clin Oncol 2014
Kaplan-Meier curve of overall survivalr
© J Clin Oncol 2014
Quality of life data was available for over 65% of patients in both arms at weeks 8/9 and 16/18, and was collected using FOSI, EORTC QLQ-OV28 and QLQ-C30 assessment tools. The primary health-related quality of life endpoint was met demonstrating more frequent ≥ 15% improvement in patient-reported abdominal/gastrointestinal symptoms with BEV+CT. An improvement in FOSI scores; physical/social/emotional functioning and global health scores occurred more frequently in the BEV+CT arm compared to the CT arm.r
Toxicity
Consistent with previous bevacizumab studies, there was a higher incidence of grade ≥ 2 proteinuria and hypertension in the BEV+CT group compared to the CT group. Grade ≥ 2 gastrointestinal perforation occurred in 2.2% of patients in the BEV+CT arm.r
The incidence of grade 3 hematologic toxicity was similar between the two treatment arms. Grade ≥ 3 abdominal pain, vomiting, fatigue, and dyspnoea, were more common in CT group.r
Grade ≥ 3 (and selected grade ≥ 2) adverse events of special interestr
© J Clin Oncol 2014