Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor

Abstract

BACKGROUND: Alveolar soft part sarcoma (ASPS), chondrosarcoma (CS), chordoma, epithelioid sarcoma, and solitary fibrous tumor (SFT) are malignant tumors that are relatively resistant to chemotherapy and for which more effective drug therapy is needed. METHODS: The 5 listed subtypes were enrolled into a single indolent sarcoma cohort in a phase 2 study of dasatinib using a Bayesian continuous monitoring rule for enrollment. The primary objective was to estimate the 6-month progression-free survival (PFS) rate according to the Choi criteria with a target of 50%. Cross-sectional imaging was performed before the start of treatment, every 2 months for 6 months, and then every 3 months during treatment. The 2-and 5-year survival rates were determined. RESULTS: One hundred sixteen patients were enrolled within 45 months, and 109 began treatment with dasatinib. The 6-month PFS rate and the median PFS were 48% and 5.8 months, respectively. The PFS rate at 6 months was highest with ASPS (62%) and lowest with SFT (30%). More than 10% of the patients with ASPS, CS, or chordoma had stable disease for more than 1 year. Collectively, for all 5 subtypes, the 2-and 5-year overall survival rates were 44% and 13%, respectively. An objective response was observed in 18% of the patients with CS or chordoma. CONCLUSIONS: Dasatinib failed to achieve control of sarcoma growth for at least 6 months in more than 50% of the patients in this trial according to the Choi tumor response criteria. An objective tumor response and prolonged stable disease was observed in >10% of patients with CS or chordoma. Cancer 2017;123:90-7.

Epithelioid sarcoma in children, adolescents, and young adults: Localized, primary metastatic and relapsed disease. Treatment results of five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry

“…Furthermore, response rate is not always an indicator of sensitivity to CHT and needs to be further evaluated as the outcome of patients with MD is poor despite response to CHT of 40%. Targeted therapies are being evaluated in current clinical trials, and the first results in adults have been published . Targeted therapy was not used in the pediatric and adolescent group analyzed.…”

A Phase II Trial of Pazopanib in Patients with Metastatic Alveolar Soft Part Sarcoma

“…Cediranib has also demonstrated encouraging efficacy in a phase II trial with an objective response rate of 35% and a disease control rate of 84% at 24 weeks . Also, >10% of the ASPS patients treated with dasatinib showed disease stabilization for >1 year . Finally, Azizi et al reported that bevacizumab, a monoclonal antibody blocking VEGF‐α, induced tumor regression in a patient with metastatic ASPS .…”

Outcome of First-Line Systemic Treatment for Unresectable Conventional, Dedifferentiated, Mesenchymal, and Clear Cell Chondrosarcoma

“…A recent phase II study with the tyrosine kinase inhibitor dasatinib included patients diagnosed with chondrosarcoma, who were incurable with conventional therapy. The median PFS for the patients in the study, enrolling all different chondrosarcoma subtypes, was 5.5 months .…”