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

Gynecol Oncol. 2012 Apr;125(1):136-40. doi: 10.1016/j.ygyno.2011.11.042. Epub 2011 Dec 2.


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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • California
  • Carcinosarcoma / drug therapy*
  • Carcinosarcoma / mortality
  • Chicago
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Genital Neoplasms, Female / drug therapy*
  • Genital Neoplasms, Female / mortality
  • Humans
  • Kaplan-Meier Estimate
  • Leiomyosarcoma / drug therapy*
  • Leiomyosarcoma / mortality
  • Middle Aged
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Treatment Outcome


  • Antineoplastic Agents
  • Recombinant Fusion Proteins
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor