On 14 November 2014, the USA Food and Drug Administration (FDA) approved bevacizumab in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for the treatment of patients with platinum resistant, recurrent epithelial ovarian, Fallopian tube, or primary peritoneal cancer.
The approval is based on the results of an international, randomised AURELIA trial. The primary endpoint was investigator-assessed progression-free survival (PFS) in patients treated with bevacizumab plus chemotherapy vs. chemotherapy alone.
The AURELIA trial enrolled 361 patients, 179 patients in bevacizumab plus chemotherapy arm, and 182 patients in chemotherapy alone arm. The chemotherapy considered paclitaxel, pegylated liposomal doxorubicin, or topotecan.
The treatment was continued until disease progression, unacceptable toxicity, and/or consent withdrawal. All enrolled patients had received no more than two prior chemotherapy regimens, had ECOG performance status of 0 to 2 and had recurred within less than six months from the most recent platinum-based therapy.
The PFS assessment demonstrated a statistically significant improvement in patients who received bevacizumab plus chemotherapy compared to those who received chemotherapy alone (hazard ratio, HR 0.38, p < 0.0001). The median PFS among patients who received bevacizumab plus chemotherapy was 6.8 months compared to 3.4 months in those who received chemotherapy alone.
There was no significant difference in overall survival (OS) (16.6 vs 13.3 months).
The trial was stratified by chemotherapy regimen. The addition of bevacizumab to paclitaxel provided the largest improvement, resulting in a 5.7 month improvement in median PFS (9.6 months vs. 3.9 months; HR = 0.47), an improvement in the overall response rate of 23% (53% vs. 30%), and a 9.2 month improvement in median OS (22.4 months vs. 13.2 months; HR = 0.64).
Among patients who received paclitaxel regimen, 97% had received paclitaxel with previous chemotherapy protocols. These exploratory analyses suggest that patients who have received prior treatment with paclitaxel may benefit from bevacizumab plus weekly paclitaxel.
The most common adverse effects in patients treated with bevacizumab plus chemotherapy were neutropaenia, peripheral sensory neuropathy, and hypertension. Gastrointestinal perforations were reported in 1.7% of patients treated with bevacizumab. Patients who had evidence of rectosigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction were excluded from this trial. These exclusions may have contributed to the relatively low rate of perforation compared to reports from earlier investigation of bevacizumab in platinum resistant ovarian cancer. Fistulae occurred in 2% of patients treated with bevacizumab comparing to none patient in chemotherapy alone arm.