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

作者：Penson Richard T; Moore Kathleen M; Fleming Gini F; Braly Patricia; Schimp Veronica; Nguyen Hoa; Matulonis Ursula A; Banerjee Susana; Haluska Paul; Gore Martin; Bodurka Diane C; Hozak Rebecca R; Joshi Adarsh; Xu Yihuan; Schwartz Jonathan D; McGuire William P^*

来源：Gynecologic Oncology, 2014, 134(3): 478-485.

DOI：10.1016/j.ygyno.2014.06.029

• Angiogenesis
• Antiangiogenic
• VEGF
• Clear cell
• Resistant

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). %26lt;br%26gt;Methods. Women who received %26gt;= 1 platinum-based chemotherapeutic regimen and had a platinum-free interval of %26lt;12 months with measurable disease were eligible. Patients received 8 mg/kg ramucirumab intravenously every 2 weeks. %26lt;br%26gt;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 %26gt;= 3) fatigue (56.7%; 33% Grade %26gt;= 3) diarrhea (283%; 1.7% Grade %26gt;= 3), hypertension (25.0%; 3.3% Grade %26gt;= 3), and nausea (20.0%; no Grade %26gt;= 3). Two patients experienced intestinal perforations (3.3% Grade %26gt;= 3). Pharmacodynamic analyses revealed changes in several circulating VEGF proteins following initial ramucirumab infusion, including increased VEGF-A, PIGF and decreased sVEGFR-2. %26lt;br%26gt;Conclusions. Although antitumor activity was observed, the predetermined efficacy endpoints were not met.

• 出版日期2014-9