Discussion
nausea, fatigue, sarcomas, toxicities, haemoptysis, angiosarcomas, advanced/metastatic, sarcoma, cavitating lung metastases, tumour, synovial sarcoma, non-adipocytic intermediate/high-grade sarcoma, advanced/unresectable
ANGIOSARCOMA, ORAL MUCOSITIS, SARCOMAS, SOFT TISSUE SARCOMAS, TUMOURS, DISEASE, ANGIOSARCOMAS, METASTASES, SARCOMA, TUMOUR, SOFT TISSUE SARCOMA, LEIOMYOSARCOMA, SYNOVIAL SARCOMA, LIVER METASTASIS, HYPERTENSION, ANGIOSARCOMAS
Until recently, all soft tissue sarcomas were treated in the same way, but in the last decade, progress has been made in identifying clinical, histological and molecular features to guide management [Angiosarcomas are rare malignant endothelial cell tumours. The standard treatments for advanced disease include anthracyclines, paclitaxel and gemcitabine, but there has been particular interest in evaluating anti-angiogenic agents in this disease [Because angiosarcomas are rare tumours, clinical trials in this patient group are challenging. Patients often have rapidly progressive disease at relapse after chemotherapy. In addition, the geographic nature of lesions can make formal response assessment challenging. For this reason, we included photographic assessment of lesions and external radiological response review was undertaken. Here, we report a formal phase II study of axitinib in four patient strata: angiosarcoma, leiomyosarcoma, synovial sarcoma and other soft tissue sarcomas. In some sarcoma subtypes, treatment with multi-kinase inhibitors has been associated with changes in tumour density rather than lesion size. Modified response criteria have been proposed by Choi et al. [Axitinib was well tolerated during Axi-STS. The AE profile has been carefully documented in previous studies, and as expected, the commonest toxicities were fatigue, hypertension, oral mucositis and nausea. However, two patients with cavitating lung metastases experienced significant haemoptysis, which was fatal in one. As described in the Methods section, we updated the original eligibility criteria so that patients were excluded if they had a history of haemoptysis and patients with cavitating lung metastases, or any metastases abutting or invading a major pulmonary blood vessel, became ineligible.The mechanism of action of anti-angiogenic agents in the treatment of soft tissue sarcoma remains uncertain but potentially involves direct inhibition of tumour cells, as well as effects on the tumour micro-environment, including interaction with the tumour immune microenvironment. Both tumour mutational analyses and studies of circulating cytokines and angiogenic factors have failed to identify validated biomarkers to predict response to these agents [As with all trials, several limitations can be identified. Of note, the details of prior systemic treatment and whether sarcomas were metastatic or locally advanced/unresectable were not collected during Axi-STS. Neither was the presence of liver metastasis separately collected, which has recently been reported as an indicator of poor prognosis [In conclusion, the Axi-STS trial has demonstrated preliminary clinical activity of the VEGFR inhibitor axitinib across four strata of patients with advanced/metastatic soft tissue sarcomas. The drug was well tolerated and merits further investigation in a phase III trial in patients with angiosarcoma, leiomyosarcoma, synovial sarcoma, and another non-adipocytic intermediate/high-grade sarcoma.