Background
Phase 3, open-label RCT (AURELIA). 361 patients with platinum-resistant recurrent ovarian, fallopian tube, or primary peritoneal cancer (progression within 6 months of platinum), ≤2 prior chemotherapy regimens, no prior anti-VEGF therapy, and no bowel involvement/fistula risk. Chemotherapy was investigator's choice: paclitaxel (weekly 80 mg/m²), pegylated liposomal doxorubicin (PLD, 40 mg/m² q4wk), or topotecan (4 mg/m² days 1/8/15 q4wk or 1.25 mg/m² days 1–5 q3wk). The platinum-resistant setting carries a historically poor prognosis with ORR of 10–20% to single-agent chemotherapy.
Interventions and follow up
Arm A: Investigator-choice chemotherapy (paclitaxel, PLD, or topotecan) + bevacizumab 10 mg/kg q2wk (with paclitaxel/topotecan) or 15 mg/kg q3wk (with PLD) until progression or toxicity
Arm B: Chemotherapy alone (same agents, same schedule)
Primary endpoint: Progression-free survival
mFollow up: 13.0 month
Arm B: Chemotherapy alone (same agents, same schedule)
Primary endpoint: Progression-free survival
mFollow up: 13.0 month
Results
PFS: 6.7 vs 3.4 months, HR 0.48 (95% CI 0.38–0.60), P<.001
ORR: 27.3% vs 11.8%, P=.001
OS: 16.6 vs 13.3 months, HR 0.85 (95% CI 0.66–1.08) — not significant
ORR: 27.3% vs 11.8%, P=.001
OS: 16.6 vs 13.3 months, HR 0.85 (95% CI 0.66–1.08) — not significant
Adverse events
Main adverse events: Grade ≥3 hypertension: 6.1% vs 0.9%. GI perforation/fistula: 2.2% vs 0% (8 bevacizumab patients, median onset 3.3 months). Grade ≥3 proteinuria: 1.0% vs 0%. Grade ≥3 thromboembolic events: 3.4% vs 0.9%. Treatment-related deaths: 3 (bevacizumab arm) vs 0. Grade ≥3 peripheral sensory neuropathy: 9.1% vs 4.4% (paclitaxel-treated patients).
Conclusions
Bevacizumab added to chemotherapy significantly improved PFS (6.7 vs 3.4 months, HR 0.48) and ORR in platinum-resistant recurrent ovarian cancer, though no OS benefit was demonstrated, and GI perforation risk was notable given the pre-treated population.
Key Limitations
Key Limitations: Open-label design. No OS benefit — post-progression crossover (67% of control arm patients received bevacizumab after progression) likely confounded the OS analysis. GI perforation occurred in 2.2% of bevacizumab patients, highlighting the importance of careful patient selection (no bowel involvement, no prior bowel surgery). The three-chemotherapy-backbone design limits interpretation of which backbone is best combined with bevacizumab; subgroup analyses suggest greatest PFS benefit with paclitaxel (HR 0.46) vs PLD or topotecan. No biomarker predictive of bevacizumab benefit was validated. Results were obtained before PARP inhibitors were available as prior therapy — the population today would be post-PARP inhibitor in many cases.
Clinical Context
AURELIA led to FDA and EMA approval of bevacizumab for platinum-resistant recurrent ovarian cancer in combination with chemotherapy. Bevacizumab + weekly paclitaxel is the most commonly used combination based on subgroup analysis. However, in the current era where patients have typically already received PARP inhibitors and bevacizumab in the frontline setting, the applicability of AURELIA to post-PARP-inhibitor recurrence is uncertain. Mirvetuximab soravtansine (SORTIE/MIRASOL trials, 2023) has emerged as a preferred option for FRα-high platinum-resistant disease.
References