An open-label single-arm phase II study of regorafenib for the treatment of angiosarcoma.

PURPOSE: Angiosarcomas represents a diverse group of aggressive high-grade vascular tumours with limited therapeutic options. We sought to determine the safety and efficacy of regorafenib, a small-molecule multikinase inhibitor, in the treatment of metastatic or locally advanced unresectable angiosarcoma. PATIENTS AND METHODS: In this single-arm multicentre, open-label phase II clinical trial, 31 patients were enrolled and received regorafenib 160 mg PO daily for 21 days of a 28-day cycle. The primary endpoint for the study was progression-free survival at 4 months. Secondary endpoints included overall survival, response rate, and safety. Patients (≥18 years) with an Eastern Cooperative Oncology Group (ECOG) score of 0-1, a life expectancy of at least 4 months who had progressed on at least one but no more than 4 prior lines of therapy were eligible. RESULTS: Of the 23 patients evaluable for efficacy, 2 had a complete response (8.7%), and 2 had a partial response (8.7%), for a total overall response rate of 17.4%. Median PFS was 5.5 months, and 12/23 patients (52.2%) had a PFS of greater than 4 months. 10/31 (32.3%) patients evaluable for toxicity had a grade 3 or higher adverse events. CONCLUSIONS: Regorafenib is a safe and active treatment for refractory metastatic and unresectable angiosarcoma. Rates of adverse events were comparable to prior studies of regorafenib for other tumour types. Regorafenib, the single agent, could be considered as therapy for patients with metastatic or unresectable AS.

Phase II study of pazopanib with oral topotecan in patients with metastatic and non-resectable soft tissue and bone sarcomas.

BACKGROUND: Pazopanib is active in refractory soft-tissue sarcoma (STS) and significantly prolongs PFS. Prior studies of combinations of metronomic topotecan with pazopanib have indicated preclinical evidence of response in patients with sarcoma. METHODS: This prospective, single arm, phase II study evaluated the efficacy of the combination of pazopanib with topotecan in patients with metastatic or unresectable non-adipocytic STS. Furthermore, it incorporated exploratory arms for osteosarcoma and liposarcoma. The primary endpoint was progression-free rate at 12 weeks in the non-adipocytic STS cohort. RESULTS: 57.5% of patients in the non-adipocytic STS cohort were progression free at 12 weeks, which did not meet the primary endpoint of the study (66%). The exploratory osteosarcoma cohort exceeded previously established phase II trial comparator data benchmark of 12% with a PFR at 12 weeks of 69.55%. Treatment with the combination of pazopanib and topotecan was accompanied by a grade 3 or 4 toxicities in most patients. CONCLUSIONS: In this prospective trial in refractory metastatic or unresectable STS and osteosarcoma, the combination of pazopanib with topotecan did not meet its primary endpoint of progression-free rate at 12 weeks. The combination of pazopanib with topotecan was associated with a high degree of toxicity.

Metastatic Myxofibrosarcoma with Durable Response to Temozolomide Followed by Atezolizumab: A Case Report.

Myxofibrosarcoma (MFS) is a well-recognized histotype of soft tissue sarcomas that generally presents with localized disease. Herein, we describe the case of a patient with metastatic MFS who experienced durable response to sixth-line therapy with temozolomide. Upon further progression, his tumor was notable for a high tumor mutational burden, and he was subsequently treated with seventh-line immunotherapy, atezolizumab, achieving a second durable response. This case highlights the role of immunotherapy after administration of alkylating agents. Review of the literature indicates that recurrent tumors treated with alkylating agents often experience hypermutation as a means of developing resistance and that checkpoint inhibitors are subsequently effective in these tumors. KEY POINTS: To the authors' knowledge, this is the first report of a patient with myxofibrosarcoma with high tumor mutational burden after administration of temozolomide monotherapy. Hypermutation may be a resistance mechanism for patients with soft tissue sarcoma who develop resistance to alkylating agents. Checkpoint inhibition may be effective therapy in patients with soft tissue sarcoma with high tumor mutational burden as a consequence of alternate systemic therapy resistance.