A phase II study of ramucirumab (IMC-1121B) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma

Abstract

ObjectiveVascular 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 6months (PFS-6) and confirmed objective response rate (ORR). MethodsWomen who received ≥1 platinum-based chemotherapeutic regimen and had a platinum-free interval of <12months with measurable disease were eligible. Patients received 8mg/kg ramucirumab intravenously every 2weeks. ResultsSixty patients were treated; one patient remained on study as of September 2013. The median age was 62years (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. ConclusionsAlthough antitumor activity was observed, the predetermined efficacy endpoints were not met.