Showing posts with label Aflibercept. Show all posts
Showing posts with label Aflibercept. Show all posts
Sunday, March 11, 2012
A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites
A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites
Objective
The recombinant fusion protein, aflibercept binds and neutralizes vascular endothelial growth factor (VEGF) A, B and placental growth factor (PlGF). Aflibercept inhibits ascites formation and reduces tumor burden in an ovarian cancer model. This open-label, single-arm, multicenter phase II study assessed the efficacy and safety of aflibercept in patients with advanced chemo-resistant epithelial ovarian cancer and symptomatic malignant ascites.
Methods
Patients who required ≥3 previous paracenteses at 1-4 paracenteses per month received intravenous aflibercept 4mg/kg every 2weeks. The primary endpoint was repeat paracentesis response rate (RPRR), with response defined as at least a two-fold increase in time to repeat paracentesis compared with the baseline interval.
Results
Ten out of 16 enrolled patients achieved a response; the RPRR was 62.5% (95% CI 35.4%–84.8%). Aflibercept was considered effective based on a hypothesis that the RPRR was ≥60%. Median time to repeat paracentesis was 76.0 (95% CI 64.0–178.0) days, which was 4.5 times longer than the baseline interval (16.8days). Median progression-free survival was 59.5 (95% CI 41.0–83.0) days. Twelve patients experienced adverse events considered related to aflibercept treatment including hypertension (7 patients), headache, anorexia, and dysphonia (3 patients each). Two patients experienced Grade 3/4 treatment-related adverse events (Grade 3 hypertension and weight loss in one patient, Grade 3 intestinal perforation in one patient).
Conclusion
Aflibercept 4mg/kg every 2weeks was effective at controlling malignant ascites, reducing the interval between repeat paracenteses. The safety profile was consistent with that reported for anti-VEGF agents.
Monday, January 30, 2012
open access: Commentary: VEGF Trap for the treatment of malignant ascites : The Lancet Oncology
"About 10% of all cases of ascites are caused by a malignant disease. In developed countries the most common neoplasm associated with ascites is ovarian cancer. The pathophysiology of malignant ascites is multifactorial, and its molecular pathogenesis is only poorly understood. Ascites formation can result from obstruction of lymph vessels by tumour cells, resulting in incomplete absorption of intraperitoneal fluid and protein,1 especially in patients with lymphoma or breast cancer. Since malignant ascites is usually an exsudate with a high protein concentration, an increased vascular permeability has been implicated in its pathogenesis.2 In addition to mechanical obstruction and cytokines, the pathophysiology of malignant ascites includes hormonal mechanisms. Because of the accumulation of ascites caused by obstructed lymph vessels, the circulating blood volume is reduced, which results in activation of the renin-angiotensin-aldosterone system that is followed by sodium retention.
Unlike the established therapeutic options for the underlying malignancy, there is no generally accepted gold standard for the management of malignant ascites....""...With respect to the clinical implications of the results (Walter Gotlieb and colleagues7 in The Lancet Oncology), symptom relief has to be weighed against discomfort and potentially life-threatening adverse events (three patients had fatal gastrointestinal complications in the aflibercept group vs one in the placebo group), since the treatment is applied to patients in a highly palliative situation. 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,8 are needed to compare the effectiveness of the different therapeutic strategies in daily clinical practice."
links to article/commentary/blogger's notes: Intravenous Aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study : The Lancet Oncology
Blogger's Note: reposted from Jan 20th due to Lancet Editorial and reference - paper is open accdess
pay specific attention to patient safety/adverse events;
related article on the (beneficial) use of Aflibercept in colorectal cancer patients (Aflibercept Improves Survival In Metastatic Colon Cancer - December 2011)
Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study Aflibercept
Interpretation
This
study shows the effectiveness of VEGF blockade in the reduction of
malignant ascites, but confirms the significant clinical risk of fatal
bowel perforation in this population of patients with very advanced
cancer. 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 view of the important pathogenetic role of VEGF in ascites formation,
the efficacy of VEGF inhibitors have also been assessed in patients
with symptomatic malignant ascites. Confirming the results of a recent
open-label single-arm phase 2 trial,6 the randomised double-blind placebo-controlled study by Walter Gotlieb and colleagues7 in The Lancet Oncology
shows the efficacy of aflibercept in patients with malignant ascites
associated with advanced ovarian cancer and can be interpreted as proof
of concept. The intervention and the control groups were homogenous,
confounding variables controlled, and bias reduced. Therefore, the study
has a high internal validity and shows the efficacy of aflibercept.
With respect to the clinical implications of the results, symptom relief
has to be weighed against discomfort and potentially life-threatening
adverse events (three patients had fatal gastrointestinal complications
in the aflibercept group vs one in the placebo group), since the
treatment is applied to patients in a highly palliative situation.
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,8 (Blogger's Note: AND patient safety) are needed to compare the effectiveness of the different therapeutic strategies in daily clinical practice."
Wednesday, December 28, 2011
Medical News: Mixed Results With (Aflibercept) Eyelea in Ovarian Cancer - in Clinical Context, Ovarian Cancer from MedPage Today
Medical News: Mixed Results With Eyelea in Ovarian Cancer - in Clinical Context, Ovarian Cancer from MedPage Today
Action Points
- The angiogenesis inhibitor aflibercept led to a decreased need for drainage of malignant ascites in patients with advanced ovarian cancer.
- Aflibercept treatment increased the likelihood of fatal bowel perforations in patients whose disease was progressing
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