Ovarian cancer remains the most lethal of all gynecologic malignancies. The American Cancer Society estimates that 21,980 women will be diagnosed with ovarian cancer this year and 14,270 women will die from this disease. Several large randomized trials have been published over the past few years looking at novel treatment agents for ovarian cancer patients.
While the most effective therapy with the longest overall survival benefit remains intraperitoneal chemotherapy with a platinum and taxane, intraperitoneal chemotherapy is not widely used due to the inconvenience of administration and the side effect profile. Investigators have been looking for new ways to treat ovarian cancer patients. Biologic agents are promising because they have few side effects and offer improved progression free survival (PFS) in phase II clinical trials.
One new trial recently published in the Journal of Clinical Oncology is the AURELIA trial (Avastin Use in Platinum Resistant Epithelial Ovarian Cancer). AURELIA was a randomized phase III clinical trial that evaluated the efficacy of bevacizumab with chemotherapy versus chemotherapy alone in platinum resistant patients. Platinum resistant patients are the most difficult to treat and have the poorest overall survival rate. Overall survival is 9-12 months and the median progression free survival is 3-4 months in this patient population1.
AURELIA was open from October 2009 to April 2011 and enrolled 361 platinum resistant patients who received less than two prior chemotherapy regimens. The AURELIA trial was not placebo controlled and it compared single agent chemotherapy with weekly paclitaxel, pegylated liposomal doxorubicin or topotecan with or without bevacizumab (Figure 1).
Patients randomized to chemotherapy alone would receive one of three single agent chemotherapy regimens at the discretion of the treating physician. If a patient on the chemotherapy alone arm progressed the patient was able to cross over and receive single agent bevacizumab. In this patient population only 7% of the patients received prior anti angiogenic therapy.
The results of the trial showed an improved PFS in patients receiving bevacizumab. The PFS was 3.4 months in the chemotherapy alone arm and 6.7 months in the chemotherapy plus bevacizumab arm (p<0.001; hazard ratio=0.42; 95% CI 0.32- 0.53), however, there was no difference in overall survival (p<0.174; 95% CI 0.66-1.08).
Gastrointestinal perforation occurred in 2.2% of the bevacizumab treated patients and in none of the chemotherapy only patients.
AURELIA is the fourth large randomized trial to look at anti angiogenic agents in advanced stage ovarian cancer and in all four trials no overall survival advantage was observed.2 Therefore, more funding and research are needed to find more effective agents to treat ovarian cancer.
Until then we need to be cognizant of the risk factors for ovarian cancer and offer prophylactic risk reducing surgeries to families at the highest risk.
1 Pujade-Lauraine, Eric et al. Bevacizumab combined with chemotherapy for platinum resistant recurrent ovarian cancer: the AURELIA open label randomized phase III trial. JCO 2014;32(13):1302-1308.
2 Liu JF and Cannistra SA. Emerging role for bevacizumab in combination with chemotherapy for patients with platinum-resistant ovarian cancer. JCO 2014;32(13):1287-1289.