January 25, 2012
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Despite reduced malignant ascites in ovarian cancer, aflibercept should be used with caution

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Final results of a phase 2 study indicated that the use of the VEGF-targeting aflibercept significantly reduced the occurrence of malignant ascites in women with advanced ovarian cancer; however, the drug confers a high risk for fatal bowel perforation.

The study was a double blind, placebo-controlled, parallel-group design that included 55 patients with advanced chemoresistant ovarian cancer and recurrent malignant ascites. The patients had undergone a median of four prior lines of chemotherapy. Patients were randomly assigned to treatment with aflibercept (Eylea, Regeneran Pharmaceuticals) 4 mg/kg every 2 weeks or placebo. The primary endpoint was time to repeat paracentesis.

Data indicated that patients assigned to aflibercept had significantly longer time to first paracentesis compared with patients assigned placebo (55.1 days vs 23.3 days; P=.0019). Median time to repeat paracentsesis was 39 days for those assigned to aflibercept and 18 days for those assigned to placebo. Two patients assigned to aflibercept went the entire 6-month double blind period without needing repeat paracentesis.

Treatment with aflibercept was not without side effects, the most common of which were dyspnea, fatigue or asthenia, and dehydration. In addition, three patients assigned to aflibercept died of bowel perforation.

In an accompanying editorial, Gerhild Becker, MD, and Hubert E. Blum, MD, of the University Medical Center Freiburg in Freiburg, Germany, wrote: “Careful patient selection could reduce the incidence of gastrointestinal perforations. However, before a general recommendation of aflibercept for the treatment of malignant ascites can be made, further studies, including comparative effectiveness research, are needed to compare the effectiveness of the different therapeutic strategies in daily clinical practice.”

For more information:

  • Gotlieb WH. Lancet Oncol. 2011;doi:10-1016/S1470-2045(22)70338-2.

PERSPECTIVE

Bradley J. Monk, MD, FACS, FACOG
Bradley J. Monk

This paper adds to our already substantial understanding of anti-angiogenesis therapy in advanced ovarian cancer. The advantages of this paper were its randomized and placebo-controlled design. There were no new findings, but again, it confirms prior observations. First, anti-VEGF therapy is active in ovarian cancer. The current study showed control of symptomatic ascites, but three randomized phase 3 trials (GOG 218, ICON-7 and OCEANS) have shown that anti-angiogenesis therapy results in durable tumor control and prolonged PFS. Second, there appears to be little or no improvement in OS with anti-VEGF therapy. The current study showed a HR of 1.02. It was underpowered, but a trend in OS would have been encouraging. Finally, the major side effect that is more common in ovarian cancer than other solid tumors is gastrointestinal perforation. One of the major predictors of perforation is multiple lines of prior chemotherapy. Among heavily pretreated women with recurrent ovarian cancer, the gastrointestinal perforation rate is about 10%, as seen in the current study. It was 11% in a previous phase 2 trial (Cannistra SA. J Clin Oncol. 2007;25:5180-5186.). So we know that aflibercept, like bevacizumab, is active in inhibiting angiogenesis since it prolongs OS in advanced colon cancer. Indeed, it also is active but toxic in ovarian cancer, again like bevacizumab. Moving forward, we need to identify biomarkers that predict efficacy to enrich the possibility of an improvement in OS. We also need to learn if anti-angiogenesis-based therapy is better used front line or second line.

– Bradley J. Monk, MD, FACS, FACOG

Professor, Division of Gynecologic Oncology,

Creighton University School of Medicine

St. Joseph’s Hospital and Medical Center

Disclosure: Dr. Monk reports no relevant financial disclosures.