VEGF is a potential therapeutic option in patients with malignant ovarian ascites. The findings of this phase II study of aflibercept, a potent inhibitor of both VEGF and placental growth factor, in the treatment of malignant ascites, have been published in the Lancet Oncology.

The study, involved 55 patients with advanced chemoresistant ovarian cancer and recurrent symptomatic malignant ascites, who had received a median of 4 (2 to 11) previous lines of chemotherapy. They were randomised to receive IV aflibercept (4 mg/kg every 2 weeks, n= 29) or placebo (n= 26), stratified by interval of time (≤2 weeks vs. >2 weeks) between the two most recent paracenteses before randomisation.

Patients took part in the double-blind period until they had a repeat paracentesis and for at least 60 days, and could also participate in an optional open-label period during which all patients received aflibercept. The primary efficacy endpoint was time to repeat paracentesis based on response during the double-blind period alone; the safety analyses included both double-blind and open-label periods.

The following findings were repeated:

• Mean time to repeat paracentesis was longer with aflibercept than with placebo (55.1 vs. 23.3 days; difference 31.8 days; p=0.0019).

• In the aflibercept group, 2 patients did not need a repeat paracentesis during 6 months of double-blind treatment.

• The most common grade 3 or 4 treatment-emergent adverse events were dyspnoea (6 [20%] aflibercept vs. 2 [8%] placebo), fatigue or asthenia (4 [13%] vs. 11 [44%]), and dehydration (3 [10%] vs. 3 [12%]).

• The frequency of fatal gastrointestinal events was higher with aflibercept (3 intestinal perforations) than with placebo (1 intestinal fistula leading to sepsis).

The researchers conclude that this preliminary study suggests effectiveness of VEGF blockade in the reduction of malignant ascites, but also confirms the significant clinical risk of fatal bowel perforation in this population of patients with very advanced cancer. They advise that “VEGF blockade should be used with caution in advanced ovarian cancer with abdominal carcinomatosis, and the benefit—risk balance should be thoroughly discussed for each patient.”

An accompanying Comment article notes that these findings can be interpreted as proof of concept and with respect to their clinical implications; symptom relief has to be weighed against discomfort and potentially life-threatening adverse events, since the treatment is applied to patients in a highly palliative situation. It suggests that careful patient selection could reduce the incidence of gastrointestinal perforations, but before a general recommendation can be made for use of aflibercept for the treatment of malignant ascites, further studies are needed to compare the effectiveness of the different therapeutic strategies in daily clinical practice.