FDA Approves Bevacizumab in Combination With Chemotherapy for Certain Cancers

　　ROCKVILLE, Md -- November 14, 2014 -- The US Food and Drug Administration (FDA) has approved bevacizumab (Avastin) solution for intravenous infusion 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.山东省肿瘤防治研究院肿瘤内科张品良

　　The approval is based on the results of an international, randomised, 2-arm trial (AURELIA) with the primary comparison of investigator-assessed progression-free survival (PFS). This trial compared bevacizumab plus chemotherapy versus chemotherapy alone. The trial enrolled 361 patients, of which 179 patients were assigned to receive bevacizumab plus chemotherapy and 182 patients were assigned to receive chemotherapy alone. The chemotherapy included paclitaxel, pegylated liposomal doxorubicin, or topotecan.

　　Treatment continued until disease progression, unacceptable toxicity, and/or consent withdrawal. All enrolled patients had received no more than 2 prior chemotherapy regimens, had ECOG performance status of 0 to 2, and had recurred within less than 6 months from the most recent platinum-based therapy.

　　The PFS assessment demonstrated a statistically significant improvement in patients who received bevacizumab plus chemotherapy compared with those who received chemotherapy alone (hazard ratio [HR], 0.38; P< .0001). The median PFS of patients who received bevacizumab plus chemotherapy was 6.8 months compared with 3.4 months for those receiving chemotherapy alone. There was no significant difference in overall survival (OS) between groups (median OS, 16.6 vs 13.3 months; HR, 0.89).

　　The trial was stratified by chemotherapy regimen. Exploratory analyses were performed by comparing the addition of bevacizumab to each chemotherapy regimen. The addition of bevacizumab to paclitaxel provided the largest improvement, resulting in a 5.7 month improvement in median PFS (9.6 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 vs 13.2 months; HR, 0.64).

　　Of the patients receiving the paclitaxel regimen, 97% had received paclitaxel with previous chemotherapy regimens. These exploratory analyses suggest that patients who have received prior treatment with paclitaxel may benefit from bevacizumab plus weekly paclitaxel.

　　The most common adverse reactions (≥15%) in patients treated with bevacizumab plus chemotherapy were neutropenia, peripheral sensory neuropathy, and hypertension. Gastrointestinal perforations were reported in 1.7% of bevacizumab-treated patients.

　　Patients who had evidence of rectosigmoid involvement by pelvic examination or bowel involvement on computed tomography scan or clinical symptoms of bowel obstruction were excluded from the trial. These exclusions may have contributed to the relatively low rate of perforation compared to reports from an earlier investigation of bevacizumab in platinum-resistant ovarian cancer. Fistulae occurred in 2% of bevacizumab-treated patients and no patients receiving chemotherapy alone.

　　The recommended bevacizumab dose is 10 mg/kg every 2 weeks in combination with one of the following intravenous chemotherapy regimens: paclitaxel, pegylated liposomal doxorubicin, or weekly topotecan. Bevacizumab 15 mg/kg every 3 weeks may be combined with topotecan (every 3 weeks).

　　SOURCE: US Food and Drug Administration