By Cameron Johnston
CHICAGO, IL -- June 4, 2007 -- A randomised study of women with platinum-resistant ovarian cancer has shown that the novel antivascular endothelial growth factor (VEGF) receptor inhibitor aflibercept, also known as VEGF-Trap, has some activity in terms of producing stable disease and reducing some of the biological markers of cancer progression.
Epithelial ovarian cancer comprises around 85% to 90% of the 22,000 new cases of ovarian cancer seen each year in the US.
The results of a small interim analysis of what is to be a larger study were presented here at the ASCO meeting on June 3rd.
Patients in the study (n = 162) had already received at least 2 prior treatments with a platinum-based regimen (cisplatin or carboplatin) as well as either topotecan or liposomal doxorubicin, which are the current standards of care. They were randomised to receive either 2 mg/kg or 4 mg/kg of VEGF-Trap administered intravenously every 2 weeks.
The interim analysis showed that there was a substantial benefit to both doses. However, this was pooled data and the final analysis may show that there was a difference between the 2. Early data report an 8% partial response rate. Tumour shrinkage was seen in 7% of patients and tumour growth stopped in 71%. At 1 month, 85% of patients had stable disease, and 41% had stable disease at 14 weeks.
Two important markers may indicate how well the drug was working. Thirteen percent of patients had at least a 50% decline in CA-125, a blood tumour marker for cancer. Also, 29% of patients had a resolution of malignant ascites, or fluid retention. Ascites are usually treated by puncturing the abdominal cavity and draining the fluid. The condition has a significant impact on the patient's quality of life, and given that they have already been heavily pretreated and have run out of treatment options, this is an important consideration.
The treatment also showed an acceptable safety profile. Hypertension was seen in 46% of patients, which was not unexpected and is usually seen with this class of drugs, while 18% of patients developed grade 3 or 4 hypertension. Headache was also common, and not unexpected, occurring in 39% of patients.
Bowel perforations were seen in less than 1% of patients. This is noteworthy because other studies with anti-VEGF compounds have shown bowel perforation occurring in as many as 11% of patients, said principal investigator William Tew, MD, assistant attending physician, department of medicine, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Dr. Tew said he was not able to explain why there were so few perforations in this trial as compared with other studies.
"Most antiangiogenesis drugs have been studied in combination with other chemotherapy agents, and there are only a handful of types of cancer, including ovarian cancer, where these drugs seem to work as single agents," he said. For this reason, VEGF-Trap may show promise for patients who have developed resistance to other forms of chemotherapy, since ovarian cancer tumours are highly dependent on new blood vessel growth to spread, and VEGF-Trap prevents this blood vessel growth.
The trial is now continuing, with the goal of recruiting 200 patients worldwide.
[Presentation title: VEGF-Trap for Patients With Recurrent Platinum-Resistant Epithelial Ovarian Cancer (EOC): Preliminary Results of a Randomized Multicenter Phase II Study. Abstract 5508]
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