OER‐073: A multicenter phase 2 study evaluating the role of pazopanib in angiosarcoma

Abstract

BACKGROUND: Angiosarcomas are rare mesenchymal sarcomas that can present as primary cutaneous or noncutaneous disease. They express a variety of vascular endothelial growth factor receptors. The authors hypothesized that the treatment of angiosarcoma with pazopanib, a multikinase inhibitor with activity against vascular endothelial growth factor receptors, would result in disease response and prolonged disease stabilization. METHODS: This was an open-label, phase 2 trial of pazopanib in patients who had incurable angiosarcoma. The co-primary end points were response according to the Response Evaluation Criteria in Solid Tumors and progression-free survival (PFS) at 3 months. The starting dose of pazopanib was 800 mg daily. RESULTS: Twenty-nine patients were accrued between 2011 and 2018, and 22 patients were evaluable for response. Toxicities were similar to those identified in prior reports. There was one partial response (3%), and the clinical benefit rate (including complete responses, partial responses, and stable disease) was 48%, which was observed more frequently in patients who had cutaneous disease. The median PFS was 14.4 weeks, and the 3-month PFS rate determined by Kaplan-Meier estimate was 54.6% (95% CI, 36.0%-82.9%), meeting the primary study objective. The Kaplan-Meier overall survival estimate was 16.1 months. CONCLUSIONS: Pazopanib therapy in patients who had incurable angiosarcoma was associated with meaningful disease control, especially in those who had cutaneous disease with limited objective responses.

Treatment for taxane‐resistant cutaneous angiosarcoma: A multicenter study of 50 Japanese cases

“…In another clinical trial, the median PFS was 4.3 months with pazopanib for chemotherapy‐resistant angiosarcoma 19 . The median PFS was 132 days (4.4 months) in the present study, suggesting that the efficacy of pazopanib is comparable to that seen in previous clinical studies, even in a Japanese cohort 18,19 . The most common G3 or more AEs was hypertension, followed by liver dysfunction, which suggests that pazopanib is tolerable for the treatment of advanced angiosarcoma 18,19 .…”

“…A recent multicenter, phase 2 study evaluating pazopanib for uncurable angiosarcoma reported median PFS of 14.4 weeks and 3-month PFS of 54.6% (95% CI 36.0-82.9%). 18 In another clinical trial, the median PFS was 4.3 months with pazopanib for chemotherapy-resistant angiosarcoma. 19 The median PFS was 132 days (4.4 months) in the present study, suggesting that the efficacy of pazopanib is comparable to that seen in previous clinical studies, even in a Japanese cohort.…”

“…Pazopanib is a small‐molecule inhibitor targeting VEGFR‐1, VEGFR‐2, VEGFR‐3, platelet‐derived growth factor receptors α and β, and c‐Kit that is approved for the treatment of sarcoma, including CAS. A recent multicenter, phase 2 study evaluating pazopanib for uncurable angiosarcoma reported median PFS of 14.4 weeks and 3‐month PFS of 54.6% (95% CI 36.0–82.9%) 18 . In another clinical trial, the median PFS was 4.3 months with pazopanib for chemotherapy‐resistant angiosarcoma 19 .…”

“…19 The median PFS was 132 days (4.4 months) in the present study, suggesting that the efficacy of pazopanib is comparable to that seen in previous clinical studies, even in a Japanese cohort. 18,19 The most common G3 or more AEs was hypertension, followed by liver dysfunction, which suggests that pazopanib is tolerable for the treatment of advanced angiosarcoma. 18,19 In contrast to previous clinical trials, the incidence of G3 or more AEs was higher in the present cohort.…”

“…18,19 The most common G3 or more AEs was hypertension, followed by liver dysfunction, which suggests that pazopanib is tolerable for the treatment of advanced angiosarcoma. 18,19 In contrast to previous clinical trials, the incidence of G3 or more AEs was higher in the present cohort. Since Japanese patients weigh less than Caucasian patients, the high frequency of G3 or more AEs might be caused by the fixed-dose regimen of pazopanib (800 mg/day).…”