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

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

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19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)478-485
Number of pages8
JournalGynecologic oncology
Volume134
Issue number3
DOIs
StatePublished - Sep 2014

Keywords

  • Angiogenesis
  • Antiangiogenic
  • Clear cell
  • Resistant
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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    Penson, R. T., Moore, K. M., Fleming, G. F., Braly, P., Schimp, V., Nguyen, H., Matulonis, U. A., Banerjee, S., Haluska, P., Gore, M., Bodurka, D. C., Hozak, R. R., Joshi, A., Xu, Y., Schwartz, J. D., & McGuire, W. P. (2014). A phase II study of ramucirumab (IMC-1121B) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma. Gynecologic oncology, 134(3), 478-485. https://doi.org/10.1016/j.ygyno.2014.06.029