AURELIA - the first randomized phase III trial of bevacizumab with standard chemotherapy in platinum-resistant ovarian cancer
The first study to show benefit with a targeted therapy and improved outcome in this group of patients
- Date : 06 Jun 2012
- Topic : Gynaecologic malignancies
Speaking on behalf of the AURELIA investigators (European ovarian cancer research groups), Dr Eric Pujade-Lauraine presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (1 - 5 June 2012) results from the first phase III trial combining bevacizumab with current standard of care - chemotherapy in the treatment of platinum-resistant recurrent ovarian cancer.
Patients eligible for the trial had ovarian cancer that progressed within 6 months of completing at least 4 cycles of platinum-based therapy and had no history of bowel complications. Chemotherapy was selected by the investigator based on each patient’s prior drug exposure, and options included pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel.
Results of AURELIA phase III study
Patients were randomly assigned to receive chemotherapy alone or in combination with bevacizumab until progression or unacceptable toxicity (182 vs 179). Those in the control arm could cross over to bevacizumab at disease progression. Median follow-up was 13.9 months for patients receiving standard chemotherapy and 13 months for the bevacizumab group. Both treatment groups had similar baseline characteristics.
Median progression-free survival (PFS) was 3.4 months for those receiving standard chemotherapy alone and 6.7 months for those receiving bevacizumab (p < 0.001). Subgroup analysis indicated that the addition of bevacizumab to standard chemotherapy improved PFS regardless of age, relapse-free interval, extent of disease, presence of ascites or type of chemotherapy administered.
The 12.6% response rate in the standard chemotherapy group was about what was expected in this patient population, whereas the response rate in the bevacizumab group was significantly improved, whether evaluated by RECIST criteria or by CA-125 levels.
The safety profile of bevacizumab was consistent with previous clinical experience. Hypertension and proteinuria (grade 2 or worse) were more frequent in the bevacizumab group, 27% compared with 8% in the control group, and 12% compared with 1%, respectively; fatigue, abdominal pain, vomiting, and dyspnea occurred less frequently in the group treated with bevacizumab. Overall, seven women receiving bevacizumab experienced gastrointestinal perforation, and six had fistulas or abscesses.
The incidence of peripheral sensory neuropathy and of hand-foot syndrome (grade 3 or worse) was higher in the bevacizumab-treated patients. In the cohort receiving pegylated liposomal doxorubicin, the time-course for the cumulative incidence of hand-foot syndrome was similar in the two study groups. Likewise, in the cohort receiving paclitaxel, the time-course for the cumulative incidence of neuropathy was similar.
This study is the first randomized phase III trial to demonstrate benefit with biologic therapy and benefit with combination therapy, rather than monotherapy, in patients with platinum-resistant ovarian cancer. The researchers concluded that bevacizumab combined with chemotherapy should be considered as a new standard of care.
A rationale for stopping phase III trials in biology driven cancer types
In abstract discussion, Dr Michael Seiden of Fox Chase Cancer Center posited that because the preponderance of ovarian cancers are serous carcinomas that have lost multiple suppressors, contain numerous somatic mutations, and have considerable genomic instability, there are not large groups of similar patients suitable for phase III trials, nor is there any compelling evidence for predictive biomarkers that would identify patients likely to benefit. In addition he offered the radical considerations of stopping all phase III trials, at least with molecularly targeted agents, deep sequencing the DNA, and instituting the requirement of submitting genomics data for each patient eligible for clinical trials.
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