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abstract:
June 8, 2016
Randomized Phase II Evaluation of Bevacizumab Versus Bevacizumab Plus Fosbretabulin in Recurrent Ovarian, Tubal, or Peritoneal Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study
Purpose The vascular
disrupting agent fosbretabulin tromethamine selectively targets
pre-existing tumor vasculature, which causes
vascular shutdown and leads to cancer cell death
and necrosis. Antiangiogenesis agents such as bevacizumab, a humanized
antivascular
endothelial growth factor monoclonal antibody,
might prevent revascularization during and after treatment with a
vascular
disrupting agent.
Patients and Methods
Patients with recurrent or persistent epithelial ovarian, tubal, or
peritoneal carcinoma, measurable or detectable disease,
and three or fewer prior regimens were randomly
assigned to bevacizumab (15 mg/kg intravenously once every 3 weeks) or
the
combination of bevacizumab (15 mg/kg) plus
fosbretabulin (60 mg/m2) intravenously once every 3 weeks
until disease progression or toxicity. Randomization was stratified by
disease status (measurable
v nonmeasurable), prior bevacizumab,
and platinum-free interval. The primary end point was progression-free
survival (PFS).
The study was designed with 80% power for a
one-sided alternative at a 10% level of significance to detect a
reduction in
the hazard by 37.5%.
Results The study enrolled 107 patients. Median PFS was 4.8 months for bevacizumab and 7.3 months for bevacizumab plus fosbretabulin
(hazard ratio, 0.69; 90% two-sided CI, 0.47 to 1.00; one-sided P
= .05). The proportion responding (overall response rate) to
bevacizumab was 28.2% among 39 patients with measurable disease
and 35.7% among 42 patients treated with the
combination. The relative probability of responding was 1.27 (90% CI,
0.74 to
2.17; one-sided P = .24). Adverse
events greater than grade 3 were more common in the combination regimen
than in bevacizumab only for hypertension
(35% v 20%). There was one grade 3 thromboembolic event in the combination arm and one intestinal fistula in the bevacizumab only
arm.
Conclusion On the
basis of the PFS, overall response rate, and tolerability of these two
antivascular therapies, further evaluation
is warranted for this chemotherapy-free regimen.
Fosbretabulin in combination with bevacizumab increases the risk of
hypertension.
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