CHMP recommends EU approval of Roche's Avastin for platinum-resistant recurrent ovarian cancer

On June 27, 2014 Roche reported that the EU Committee for Medicinal Products for Human Use (CHMP) recommended that the European Commission approve the use of Avastin (bevacizumab) in combination with chemotherapy as a treatment for women with ovarian cancer that is resistant to platinum-containing chemotherapy (Press release Hoffmann-La Roche, JUN 26, 2014, View Source [SID:1234500690]). Ovarian cancer has the highest mortality rate of all gynaecological cancers.1 Of the 230,000 women diagnosed worldwide each year many will have advanced disease that will return after initial treatment.

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"Women with platinum-resistant ovarian cancer have limited medicines available for their difficult disease," said Sandra Horning M.D., Chief Medical Officer and Head, Global Product Development. "EU approval of Avastin for platinum-resistant ovarian cancer would be an important step in helping these women live longer without their disease progressing, and we look forward to receiving the final decision from the European Commission in the coming months."

When treating recurrent ovarian cancer, the time between receiving the last dose of platinum-based chemotherapy and disease recurrence is used to help determine the choice of chemotherapy used in the next line of treatment. Patients are said to have ‘platinum-resistant’ disease if their disease worsens between one and six months following completion of their platinum-based chemotherapy, and ‘platinum-sensitive’ disease if it worsens more than six months after. A quarter of those who relapse after initial treatment – nearly 60,000 women a year globally – will have platinum-resistant cancer, the most difficult to treat form of the disease. Median overall survival of patients with platinum-resistant ovarian cancer is approximately 12 months, and novel strategies are needed.

Ovarian cancer is associated with high concentrations of vascular endothelial growth factor (VEGF), a protein linked to tumour growth and spread. Studies have shown a correlation between a high concentration of VEGF and ascites development (excess fluid in the abdominal cavity), disease worsening, and a poorer prognosis in women with ovarian cancer. Avastin is designed to specifically target VEGF and is currently the only targeted therapy approved by the European Medicines Agency (EMA) for ovarian cancer. Avastin is EU approved as a front-line (first line following surgery) treatment of advanced ovarian cancer, and as a treatment for recurrent, platinum-sensitive ovarian cancer.

The new EU filing was based on results of the phase III AURELIA study which involved women with recurrent, platinum-resistant ovarian cancer who received either chemotherapy (weekly paclitaxel, topotecan or pegylated liposomal doxorubicin) or Avastin added to chemotherapy.4 Results showed that at a median follow-up of 13 months for women who had received chemotherapy alone and 13.9 months for those who had received the combination, the addition of Avastin to chemotherapy gave a clinically meaningful benefit, nearly doubling the median PFS from 3.4 months to 6.7 months (HR=0.38, p<0.0001).4,6 AURELIA is the fourth phase III study of Avastin in ovarian cancer (following GOG 0218, ICON7 and OCEANS) to show that adding Avastin to chemotherapy significantly increased the time women with ovarian cancer lived without their disease getting worse.
AURELIA additional study results

Women with recurrent, platinum-resistant ovarian cancer who received Avastin in combination with chemotherapy (weekly paclitaxel, topotecan or pegylated liposomal doxorubicin) had a median overall survival of 16.6 months compared to 13.3 months for women treated with chemotherapy alone (HR=0.87, p=0.27).
In addition, women who received Avastin in combination with chemotherapy had a significantly higher rate of tumour shrinkage (objective response rate, ORR) compared to women who received chemotherapy alone (28.2 percent versus 12.5 percent, p=0.0007).
The results of prespecified Quality of Life (QoL) analyses indicated that the benefits of Avastin in AURELIA extended beyond the prolongation of PFS to include greater improvements in ovarian cancer associated abdominal/gastrointestinal symptoms.
No new safety findings were observed in the AURELIA study and adverse events were consistent with those seen in previous trials of Avastin across tumour types for approved indications.4

About the AURELIA study

AURELIA is a multicentre, randomised, open-label, two-arm phase III study in 361 women with platinum-resistant recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer. Women in AURELIA had received no more than two anticancer regimens prior to enrolment in the trial. The trial was designed to evaluate Avastin (10mg/kg every two weeks or 15mg/kg every three weeks) in combination with standard chemotherapy (either weekly paclitaxel or topotecan or pegylated liposomal doxorubicin) compared to standard chemotherapy alone.

The trial was set up in cooperation with the Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO) and was conducted by the international network of the Gynecologic Cancer Intergroup (GCIG) and the pan-European Network of Gynaecological Oncological Trial Groups (ENGOT). The primary endpoint of the study was progression-free survival. The secondary endpoints of the study included overall survival, objective response rate, Quality of Life, safety and tolerability.