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 4 mg/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.