A phase II study of aflibercept (VEGF trap) in recurrent or metastatic gynecologic soft-tissue sarcomas: A study of the Princess Margaret Hospital Phase II Consortium
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5591 Background: Targeting angiogenesis and vascular endothelial growth factor (VEGF) represents a promising approach to treat highly vascular tumors, like gynecologic sarcomas. Aflibercept, a long-acting inhibitor of VEGF signaling, potently binds and inactivates VEGF, thus blocking tumor angiogenesis and growth. Methods: This is a single-arm, open-label, two-stage phase II clinical trial designed to evaluate the efficacy and toxicity of aflibercept as treatment for patients (pts) with recurrent, or metastatic gynecologic soft tissue sarcoma. Aflibercept was administered at 4 mg/kg IV every 2 weeks and pts had radiologic imaging performed every 8 weeks. The primary endpoints were response rate and prolonged stable disease. Results: Twenty-five pts with leiomyosarcoma of the uterus and 13 pts with carcinosarcoma of the uterus were enrolled in 2 cohorts. In the leiomyosarcoma group, 24/25 pts had an ECOG of <1, most pts (22/25) had <1 previous lines of treatment and 7/25 pts had prior radiotherapy. A total of 149 cycles were administered for this group, with a median of 4 (range 2–28). In the carcinosarcoma group, 10/13 pts had an ECOG of <1, most pts (12/13) had <1 previous lines of treatment and 5/13 pts had prior radiotherapy. A total of 31 cycles were administered with a median of 3 (range 1–4). The most frequent adverse events experienced by all pts, of any grade, were fatigue 71% pts, constipation 53% and hypertension 39% . The most frequent grade 3 or higher, adverse events were hypertension 18%, fatigue 13% and lymphopenia 8%. Eight pts with leiomyosarcoma had stable disease (4pts > 6 mo). No reponses were seen in either cohort and no stable disease was seen in the carcinosarcoma group. Median overall survival was 15.1 mo (95% CI: 8.5 - not reached) for the leiomyosarcoma cohort and 3.1 mo for the carcinosarcoma cohort (95% CI: 1.9 - not reached). The requirements to proceed to stage 2, in leiomyosarcoma, were met after more than 2/21 patients had > 6 mo PFS. Carcinosarcoma cohort has not finished stage 1 and both cohorts continue accrual. Conclusions: VEGF-trap was well tolerated in this pt population with acceptable side effects. Initial efficacy data suggests modest activity, particularly in patients with leiomyosarcoma. [Table: see text]
