Efficacy and safety of trabectedin for patients with unresectable and relapsed soft-tissue sarcoma in Japan: A Japanese Musculoskeletal Oncology Group study.

Abstract

Although initial trabectedin (1.2mg/m2 ) is safe and effective for patients with translocation-related sarcoma (TRS) in Japan, its efficacy in other types of soft-tissue sarcomas (STSs) remains unknown. This study retrospectively investigated its efficacy and safety through postmarketing surveillance of trabectedin in patients with unresectable and relapsed STS. One hundred forty patients received intravenous trabectedin (1.2mg/m2 on day 1 every 21days) over the course of 24hours. The primary endpoint was the efficacy and safety of trabectedin. Grade 3 or higher adverse events occurred in 100 patients (71%) and included hepatotoxicity (37.8%), neutropenia (32.8%), and rhabdomyolysis (3.6%). Patients at high risk for grade 3 or higher rhabdomyolysis (36%) were classified by height (≥170.3cm) and age (≤32years) through a classification and regression tree model (area under the curve, 0.9). The overall median progression-free survival (PFS) was 3.7months; with respect to the histological type, the median PFS was 17.4months for myxoid liposarcoma, 4.9months for leiomyosarcoma, 5.6months for synovial sarcoma, and 3.7months for dedifferentiated liposarcoma. Histological type (liposarcoma/leiomyosarcoma [L-sarcoma] and TRS) and grade 3 neutropenia (but not grade 4) were associated with significantly improved PFS after trabectedin treatment (P=.003, P=.04, and P=.001). The median growth modulation index (GMI) was 0.91; 37 patients (36.7%) experienced a GMI>1.33, and among patients with solitary fibrous tumors and undifferentiated pleomorphic sarcoma, 60% and 42.9%, respectively, had a GMI>1.33. The median overall survival (OS) was 16.4months. A GMI>1.33 was associated with significantly improved OS (P=.0006). Initial trabectedin at 1.2mg/m2 has clinically meaningful benefits for patients with L-sarcoma and certain histological subtypes of TRS.