According to a novel phase II randomized study published Online First in The Lancet Oncology, a new anti-VEGF drug aflibercept that obstructs the action of vascular endothelial growth factor (VEGF) can prevent malignant ascites (excessive fluid in the abdomen that contains cancer cells), a prevalent and painful complication of advanced ovarian cancer from developing.

Lead author Walter Gotlieb from Jewish General Hospital, McGill University, Montreal, Canada, explains:

“Anti-VEGF treatments such as aflibercept appear to reduce the formation of malignant ascites and could dramatically improve the quality of life for patients with this debilitating complication. But clinicians must exercise caution in their use of aflibercept because of the significantly increased risk of fatal bowel perforation.”

Two-thirds of individuals with ovarian cancer are diagnosed with late-stage disease, prevalently connected with malignant ascites. The cancerous cells generate VEGF, which increases the permeability of capillaries, increasing the flow of fluids into the abdomen, and forming ascites. The typical treatment, paracentesis involves inserting a needle into the abdomen to drain excess fluid. Although this treatment can provide the patient with temporary relief it is invasive and unpleasant.

Aflibercept is a strong inhibitor of both placental growth factor and VEGF. According to preclinical investigations and a pilot study the medication may be effective in preventing malignant ascites developing.

In this article the investigators reveal the results of a phase II randomized study, which examined if aflibercept might delay paracentesis and to analyze the safety of VEGF inhibition in individuals suffering with advanced ovarian cancer and recurrent malignant ascites.

55 individuals from 6 nations who underwent at least two previous chemotherapy regimens and whose tumors had become chemoresistant were enrolled to participate in the investigation. The researchers randomly assigned participants to two groups, 26 received placebo while 29 received aflibercept.

Participants in the aflibercept group time to repeat paracentesis more than doubled (55 days) compared to those who received placebo (23 days). Furthermore, repeat paracentesis was not required during the six months of treatment for two individuals in the aflibercept group. In addition, those who received aflibercept reported greater improvement in ascite symptoms compared to those who received placebo.

The most prevalent treatment associated side effects were:

  • Fatigue or asthenia (4 [13%] aflibercept vs 11 [44%] placebo])
  • Dehydration (3 [10%] vs 3 [12%])
  • Dyspnoea (6 [20%] vs 2 [8%])

In the aflibercept group three deaths occurred from bowel perforations, and one intestinal fistula leading to sepsis and death in the placebo group.

The researchers say:

“The trial clearly shows the effectiveness of VEGF blockade in the reduction of ascites formation but confirms the significant clinical risk of fatal bowel perforation in this population of patients with very advanced cancer.”

They conclude:

“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.”

In an associated comment, Dr Gerhild Becker and H E Blum from University Hospital Freiburg, Freiburg, Germany explains:

“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.”

Written by Grace Rattue