June 14, 2007 (Chicago) -- Preliminary data suggest that vascular endothelial growth factor (VEGF) trap ( Aflibercept, Regeneron and Sanofi-Aventis) is active in patients with recurrent chemotherapy-resistant epithelial ovarian cancer. Reporting here at the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting, researchers say the targeted therapy may represent an important new option for patients who have received 3 or 4 prior chemotherapy regimens and have become resistant to platinum-based agents.
"Ovarian cancer groups should be very excited," Dean Bajorin, MD, from Memorial Sloan-Kettering Cancer Center, in New York, and moderator of a news conference outlining the findings, told Medscape. "There have been no defined therapeutic options for women who have failed all therapies," he added. "They have now identified an active drug for use in heavily pretreated patients."
"Most antiangiogenesis drugs have been studied in combination with other chemotherapy agents," lead investigator William Tew, MD, from Memorial Sloan-Kettering Cancer Center, told reporters. "There are only a handful of diseases for which these drugs seem to work as a single agent, and ovarian cancer, because of its high dependence on blood vessel growth to spread, seems to be 1 of them. As a result, VEGF trap shows potential for patients who have developed resistance to other chemotherapy agents."
Discussing the findings after the presentation, Elizabeth Eisenhauer, MD, from the National Cancer Institute of Canada Clinical Trials Group, in Toronto, agreed that VEGF trap shows some evidence of activity. "The observations confirm the importance of angiogenesis inhibitors as agents of interest in ovarian cancer," she told meeting attendees. "The toxic effects are similar to those reported with other angiogenesis inhibitors, including some risk of bowel perforation."
But Dr. Eisenhauer was critical of the presentation and questioned why the results were being shown so early at ASCO. "Why now?" she said during her talk, "With ongoing accrual and blinded results, why not wait to present findings from a final sample?"
Trial Status
|
Patients
|
n
|
|
Accrual goal
|
200
|
|
Randomized
|
162
|
|
Discontinued
|
127
|
|
Stopped due to progression
|
93
|
|
Stopped due to toxicity
|
17
|
|
Stopped for other reasons
|
17
|
|
Ongoing treatment
|
35
|
During a news conference about the trial, Dr. Tew emphasized to reporters that the findings are preliminary. The presentation is based on investigator review and will be analyzed by an independent third party in the final analysis.
The randomized, multicenter, double-blind, phase 2 study looked at patients from 44 sites in 12 countries in Europe, the United States, and Canada. Patients with recurrent chemotherapy-resistant epithelial ovarian cancer received intravenous VEGF trap 2 mg/kg or 4 mg/kg every 2 weeks.
Efficacy: Preliminary Data From Blinded Pool Summary (n=162)
|
Outcome
|
n (%)
|
|
Radiological partial response
|
13 (8)
|
|
A 50% decline in CA-125
|
21 (13)
|
|
Stable disease + partial response
|
|
|
138 (85)
|
|
67 (41)
|
|
25 (15)
|
|
7 (4)
|
Safety Profile (n=162)
|
Adverse Events
|
All Grades (%)
|
Grade 3/4 (%)
|
|
Hypertension
|
46
|
18
|
|
Headache
|
39
|
4
|
|
Dysphoria
|
35
|
1
|
|
Fatigue
|
28
|
3
|
|
Nausea
|
21
|
0
|
|
Asthenia
|
20
|
4
|
|
Proteinuria
|
18
|
7
|
|
Arthralgia
|
16
|
1
|
|
Anorexia
|
12
|
1
|
|
Abdominal pain
|
11
|
1
|
During an interview with Medscape, Dr. Bajorin noted that VEGF trap demonstrates an acceptable safety profile with a low incidence of gastrointestinal perforations. He called the rate of 1% encouraging.
Speaking at the meeting, Dr. Eisenhauer said both groups of the trial should continue. She suggested that investigators use the information on efficacy and toxicity in the final sample to determine the best dose to take forward. Accrual for the trial is planned to continue to 200 patients.
"Ovarian cancer may be unusual among solid tumors because vascular-targeting agents like VEGF trap appear to have significant single-agent activity," senior investigator David Spriggs, MD, also from Memorial Sloan-Kettering, said in a news release. "In most solid tumors, the efficacy of VEGF targeting is likely to be further enhanced by combining it with classic chemotherapy agents."
But, Dr. Eisenhauer concluded, "Future gains in ovarian cancer will likely to come from novel agents exploiting molecular defects."
American Society of Clinical Oncology 43rd Annual Meeting: Abstract 5508. Presented June 3, 2007.
Medscape Medical News © 2007 Medscape
Cite this: Allison Gandey. VEGF Trap Showing Potential in Advanced Ovarian Cancer - Medscape - Jun 14, 2007.
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