title: A phase II study single agent of aflibercept (VEGF Trap) in patients with recurrent or metastatic gynecologic carcinosarcomas and uterine leiomyosarcoma. A trial of the Princess Margaret Hospital, Chicago and California Cancer Phase II Consortia.
abstract: OBJECTIVE
  The aim of this multi-institutional non randomized phase II trial was to determine the efficacy and safety of single agent aflibercept (VEGF Trap), a recombinant fusion protein that blocks multiple vascular endothelial growth factor isoforms, in women with gynecologic soft tissue sarcoma.
  
  
  METHODS
  Patients were enrolled in two cohorts each with Simon two stage designs: uterine leiomyosarcoma and carcinosarcoma of endometrial, ovarian or fallopian tube origin. Eligibility criteria included ≤2 prior lines of chemotherapy for metastatic disease and ECOG performance status of ≤2. Aflibercept 4mg/kg was administered intravenously on day 1 of a 14 day cycle. Primary endpoints were objective response and disease stabilization (Progression Free Survival (PFS) at 6 months).
  
  
  RESULTS
  41 patients with uterine leiomyosarcoma and 22 patients with carcinosarcoma (19 uterine, 3 ovarian) were enrolled on study. In the leiomyosarcoma cohort, eleven (27%) patients had stable disease (SD), 4 with SD lasting at least 24 weeks. The 6 month PFS was 17%, with median time to progression (TTP) of 1.8 (95% CI:1.6-2.1) months. In the carcinosarcoma cohort, two (9%) patients had SD, one lasting >24 weeks, median TTP was 1.6 months (95%CI: 1.1-1.7) No partial responses were observed in patients from either cohort. Grade 3 or more aflibercept related toxicity was uncommon and included hypertension, fatigue, headache and abdominal pain.
  
  
  CONCLUSIONS
  Single agent aflibercept has modest activity in patients with uterine leiomyosarcoma and minimal activity in women with carcinosarcoma.
authors.affiliation: Princess Margaret Hospital, Ontario, Canada.
authors.forename: H J
authors.initials: HJ
authors.lastname: Mackay
authors.forename: R J
authors.initials: RJ
authors.lastname: Buckanovich
authors.forename: H
authors.initials: H
authors.lastname: Hirte
authors.forename: R
authors.initials: R
authors.lastname: Correa
authors.forename: P
authors.initials: P
authors.lastname: Hoskins
authors.forename: J
authors.initials: J
authors.lastname: Biagi
authors.forename: L P
authors.initials: LP
authors.lastname: Martin
authors.forename: G F
authors.initials: GF
authors.lastname: Fleming
authors.forename: R
authors.initials: R
authors.lastname: Morgan
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Polintan
authors.forename: A M
authors.initials: AM
authors.lastname: Oza
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002140:California; D002296:Carcinosarcoma / Q000188:drug therapy* / Q000401:mortality; D002641:Chicago; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor