title: A phase II study of ramucirumab (IMC-1121B) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.
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.
authors.affiliation: Massachusetts General Hospital for the Dana-Farber/Harvard Cancer Center, Boston, MA, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Penson
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Moore
authors.affiliation: University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.affiliation: Hematology and Oncology Specialists, LLC, Marrero, LA, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Braly
authors.affiliation: MD Anderson Cancer Center, Orlando, FL, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Schimp
authors.affiliation: Gynecologic Oncology Associates, Inc., Hollywood, USA.
authors.forename: Hoa
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Matulonis
authors.affiliation: Royal Marsden Hospital, Surrey, England, UK.
authors.forename: Susana
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Haluska
authors.affiliation: Royal Marsden Hospital, London, England, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Gore
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Diane C
authors.initials: DC
authors.lastname: Bodurka
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Hozak
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Adarsh
authors.initials: A
authors.lastname: Joshi
authors.affiliation: ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, Bridgewater, NJ, USA.
authors.forename: Yihuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, Bridgewater, NJ, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Schwartz
authors.affiliation: Inova Fairfax Hospital, Falls Church, VA, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: McGuire
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002277:Carcinoma / Q000188:drug therapy*; D018572:Disease-Free Survival; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D055815:Young Adult; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000096662:Ramucirumab
keywords: Angiogenesis; Antiangiogenic; Clear cell; Resistant; VEGF