SUMMARY: AURELIA is a multicenter, randomized, open-label, two-arm Phase III study in which 361 women with platinum-resistant recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer were enrolled. These patients had disease progression within six months of their platinum based chemotherapy. Patients were randomly assigned to receive AVASTIN® (Bevacizumab) in combination with chemotherapy which included weekly paclitaxel, topotecan or pegylated liposomal doxorubicin or chemotherapy alone. The primary end point was Progression Free Survival. There was a 52% reduction in the risk of progression in those who received AVASTIN® plus chemotherapy compared to those who received chemotherapy alone (HR=0.48, P<0.001). Further, there was a significantly higher objective response rate in the AVASTIN® group compared to those who received chemotherapy alone (30.9 percent vs. 12.6 percent, p=0.001). Pujade-Lauraine E, Hilpert F, Weber B, et al. J Clin Oncol 30, 2012 (suppl; abstr LBA5002)
SUMMARY: The role of Bevacizumab (AVASTIN®) in the treatment of advanced ovarian cancer was evaluated in a large randomized double blind phase III trial. One thousand eight hundred and seventy three (1873) patients with stage III or IV disease, who were treatment naïve, were randomly assigned to one of three treatment groups – standard chemotherapy with paclitaxel and carboplatin given along with a placebo followed maintenance treatment with a placebo, standard chemotherapy given along with AVASTIN® followed by maintenance treatment with a placebo or standard chemotherapy given along with AVASTIN® followed by maintenance treatment with AVASTIN®. Patients receiving standard chemotherapy along with AVASTIN® followed by maintenance AVASTIN® had a median Progression Free Survival of 14.1 months compared to 10.3 months for those who received standard chemotherapy alone. Interestingly, outcomes in patients receiving standard chemotherapy along with AVASTIN® followed by placebo maintenance did no better than those who received standard chemotherapy alone. To date, addition of AVASTIN® to standard chemotherapy followed by AVASTIN® maintenance has not resulted in significant improvement in overall survival. J Clin Oncol 28:18s, 2010 (suppl; abstr LBA1)
Ovarian cancer is potentially curable if diagnosed at an early stage. Unfortunately only 20-25% of the patients are diagnosed with early stage disease, ie. Stage I and Stage II. Majority of the patients with ovarian cancer are diagnosed with Stage III or Stage IV disease. Screening postmenopausal women or those considered to be at high risk therefore makes perfect sense. A British study presented at ASCO 2010, screened postmenopausal women, considered not to be at high risk,with a combination of pelvic ultrasound and CA-125. Preliminary data is very promising and screening techniques were able to diagnose ovarian cancer at an earlier stage.
It is possible that we may have an algorithm to screen for ovarian cancer, in the very near future.
Taxanes were first introduced in the mid 1990’s for the first line treatment of ovarian cancer. There has since been no real progress made. However recent data presented at ESMO (European Society for Medical Oncology) 2010, shed light on the benefit of adding Bevacizumab to standard chemotherapy. In the ICON 7 trial, 1,528 women with high risk, early or advanced stage ovarian cancer were randomized to receive either 6 cycles of standard chemotherapy with Carboplatin and Paclitaxel or Carboplatin and Paclitaxel given along with Bevacizumab, followed by maintenance Bevacizumab for an additional 12 cycles.
There was a significant improvement in the median progression free survival in the Bevacizumab group. Patients with poor risk features benefited the most. So, after over 15 years of drought, we are now seeing progress made, in the treatment of ovarian cancer. It is not clear at this time however, if this three drug combination will improve Overall Survival.