Gynecol Oncol. 2014 Sep;134(3):478-85. doi: 10.1016/j.ygyno.2014.06.029. Epub 2014 Jul 10.
A
phase II study of ramucirumab (IMC-1121B) in the treatment of
persistent or recurrent epithelial ovarian, fallopian tube or primary
peritoneal carcinoma.
OBJECTIVE:
Vascular
endothelial growth factor (VEGF) receptor-mediated signaling
contributes to ovarian cancer pathogenesis. Elevated VEGF expression is
associated with poor clinical outcomes. We investigated
ramucirumab, a
fully human anti-VEGFR-2 antibody, in patients with persistent or
recurrent epithelial ovarian, fallopian tube, or primary peritoneal
carcinoma. Primary endpoints were progression-free survival at 6 months
(PFS-6) and confirmed objective response rate (ORR).
METHODS:
Women
who received ≥ 1 platinum-based chemotherapeutic regimen and had a
platinum-free interval of <12 months with measurable disease were
eligible. Patients received 8 mg/kg ramucirumab intravenously every 2
weeks.
RESULTS:
Sixty
patients were treated; one patient remained on study as of September
2013. The median age was 62 years (range: 27-80), and median number of
prior regimens was 3. Forty-five (75%) patients had platinum
refractory/resistant disease. Thirty-nine patients (65.0%) had serous
tumors. PFS-6 was 25.0% (n=15/60, 95% CI: 14.7-37.9%). Best overall
response was: partial response 5.0% (n=3/60), stable disease 56.7%
(n=34/60), and progressive disease 33.3% (n=20/60). The most common
treatment-emergent adverse events possibly related to study drug were
headache (65.0%; 10.0% Grade ≥ 3), fatigue (56.7%; 3.3% Grade ≥ 3),
diarrhea (28.3%; 1.7% Grade ≥ 3), hypertension (25.0%; 3.3% Grade ≥ 3),
and nausea (20.0%; no Grade ≥ 3).
Two patients experienced intestinal
perforations (3.3% Grade ≥ 3). Pharmacodynamic analyses revealed changes
in several circulating VEGF proteins following initial ramucirumab
infusion, including increased VEGF-A, PlGF and decreased sVEGFR-2.
CONCLUSIONS:
Although antitumor activity was observed, the predetermined efficacy endpoints were not met.
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