Olaratumab is a?humanised monoclonal antibody to PDGFa. histological subtype . One?CR and 4?PR were observed in 34?patients with angiosarcoma. The Rabbit polyclonal to APCDD1 median PFS of the vascular sarcoma cohort, which included 2?patients with solitary fibrous tumour and 1?patient with giant haemangioma, was 3.8?months. In comparison, the median PFS across all sarcoma subtypes was 3.2?months. Angiosarcoma response to sorafenib 400?mg bd was studied by the French Sarcoma Group in two patient cohorts: 26?patients with cutaneous angiosarcoma and 15?patients with visceral disease . The primary endpoint for this study was the 9?month progression-free rate. Only 2?patients, 1?from each cohort, were progression free at 9?months. The median PFS was 1.8?and 3.8?months for cutaneous and visceral disease respectively. STS response to pazopanib (a?VEGFR, fibroblast growth factor receptor [FGFR] and platelet derived growth factor receptor [PDGFR] inhibitor) 800 mg omni die (od) was studied in the phase?II?EORTC 62043 , and subsequent randomised placebo-controlled phase?III?EORTC 62072 (PALETTE) study . The median PFS of patients that received pazopanib in the PALETTE study was 4.6?months, compared to 1.6?months in patients that received placebo (HR 0.31, 95% CI 0.24C0.40; em p /em ? 0.0001). Angiosarcoma response to pazopanib was not reported separately; however a?retrospective analysis of a?cohort of 40?angiosarcoma patients treated with pazopanib in either the EORTC 62043 study, the PALETTE study, or in program clinical practice, reported a?20% response rate and median PFS of 3.0?months . There were no significant differences observed between different subtypes of angiosarcoma in response to pazopanib. Angiosarcoma response to axitinib Loganic acid (a?VEGFR, PDGFR and KIT inhibitor) 5 mg bd was recently studied within a?UK histologically stratified phase?II study (“type”:”clinical-trial”,”attrs”:”text”:”NCT01140737″,”term_id”:”NCT01140737″NCT01140737), which also included cohorts for patients with advanced leiomyosarcoma, synovial sarcoma and other STS histologies. Preliminary results from the angiosarcoma cohort were reported at the Connective Tissue Oncology Society 2016 annual meeting; the response rate was 10%, 12?week non-progression rate 42%, and median PFS 4.2?months . Agents targeting non-VEGF angiogenic pathways Angiopoietin 1/2 Angiosarcoma response to weekly trebananib (30?mg/kg), an angiopoietin-1 and -2 peptibody, was studied in a?small single arm phase?II?study. No responses were observed and the median PFS was 1.6?months. STS response to regorafenib 160?mg od, a?multi-kinase inhibitor targeting VEGFR, PDGFR, Kit, RET and Raf-1, as well as TIE2, an angiopoietin receptor, was studied in a?histologically stratified, randomised, placebo-controlled phase?II?study . Much like STS response to pazopanib, an unplanned pooled analysis of non-adipocytic STS cohorts reported a?median PFS 4.0?months with regorafenib compared Loganic acid to 1.0?months with placebo (HR 0.36, 95% CI 0.25C0.53; em p /em ? 0.0001). Angiosarcoma response to regorafenib was not reported, but a?individual study of regorafenib for advanced angiosarcoma is currently ongoing (“type”:”clinical-trial”,”attrs”:”text”:”NCT02048722″,”term_id”:”NCT02048722″NCT02048722). PDGF In addition to VEGFR, pazopanib, regorafenib and axitinib also inhibit PDGFR. Olaratumab is usually a?humanised monoclonal antibody to PDGFa. Promising results were observed in a?randomised phase?I/II?study of olaratumab in combination with doxorubicin as first-line treatment for advanced STS ; a?phase?III?study recently completed recruitment and results are eagerly awaited (“type”:”clinical-trial”,”attrs”:”text”:”NCT 02451943″,”term_id”:”NCT02451943″NCT 02451943). Angiosarcoma response to olaratumab has not been reported. Endoglin The transforming growth factor (TGF)- and bone morphogenetic protein (BMP)-9 receptors activin receptor-line kinase (ALK)-1 and endoglin are required for normal vascular development, and are highly expressed Loganic acid on tumour endothelial cells . TRC105 is a?chimeric monoclonal antibody that binds endoglin . Non-adipocytic STS response to TRC105 in combination with pazopanib was studied in a?phase?I/II?study ; response to treatment was observed in 8/9?angiosarcoma patients, including two durable CR. A?randomised phase?III?trial of pazopanib? TRC105 in angiosarcoma recently opened to recruitment (“type”:”clinical-trial”,”attrs”:”text”:”NCT02979899″,”term_id”:”NCT02979899″NCT02979899). Other vascular targeted agents Thalidomide Angiosarcoma response to thalidomide, an immunomodulatory agent.