Bevacizumab (Avastin®) is a recombinant monoclonal antibody which prevents the growth of tumour blood vessels. It is indicated for the treatment of patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and no prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor–targeted agents.
The EMA approved bevacizumab for platinum-resistant, epithelial ovarian cancer on 31st July 2014.
This decision was based on the AURELIA trial - an open-label, randomised phase III trial. 361 patients were randomised either to a single-agent chemotherapy (n=182) or to a chemotherapy in combination with bevacizumab (n=179).
This trial demonstrated a significant improvement in progression-free survival for platinum-resistant ovarian cancer patients treated with bevacizumab and chemotherapy in comparison to chemotherapy alone. The administration of bevacizumab in combination with paclitaxel, topotecan or pegylated liposomal doxorubicin resulted in an absolute gain in median PFS of 3.3 months and reduced the risk of progression or death by 52%. No difference was observed for overall survival.
Adverse events were overall more frequent in the combination group. Grade 3 adverse events such as gastrointestinal (GI) perforation, proteinuria, fistula/abscess and reversible posterior leukoencephalopathy syndrom occurred only in the bevacizumab arm. Hypertension and proteinuria grade ≥ 2 were more common in the treatment arm with bevacizumab. 20% of patients treated with this regimen had hypertension and 2% proteinuria.
Some indications for a positive impact on QoL can be derived from patients included in the AURELIA trial, since more patients in the bevacizumab arm experienced a ≥ 15% improvement in abdominal/GI symptoms.
Even though this phase III trial has found some improved results in terms of progression-free survival for bevacizumab in addition to chemotherapy, the question posed is when and in which setting bevacizumab can yield the greatest benefit. Foremost, monotherapy may be less toxic than combinations with cytotoxic regimens. Furthermore, the efficacy of bevacizumab in patients previously treated with VEGF inhibitors remains unknown.