Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial

Objective Trabectedin demonstrated significantly improved disease control in leiomyosarcoma and liposarcoma patients in a global phase 3 trial (NCT01343277). A post hoc analysis was conducted to assess the efficacy and safety of trabectedin or dacarbazine in women with uterine leiomyosarcoma (uLMS), the largest subgroup of enrolled patients (40%). Methods Of 577 patients randomized 2:1 to receive trabectedin 1.5 mg/m² by 24-hour IV infusion or dacarbazine 1 g/m² by 20–120-minute IV infusion once every three weeks, 232 had uLMS (trabectedin: 144; dacarbazine: 88). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR: complete responses + partial responses + stable disease [SD] for at least 18 weeks), duration of response (DOR), and safety. Results PFS for trabectedin was 4.0 months compared with 1.5 months for dacarbazine (hazard ratio [HR] = 0.57; 95% CI 0.41–0.81; P = 0.0012). OS was similar (trabectedin 13.4 months vs. dacarbazine 12.9 months, HR = 0.89; 95% CI 0.65–1.24; P = 0.51) between groups. ORR was 11% with trabectedin vs. 9% with dacarbazine (P = 0.82). CBR for trabectedin was 31% vs. 18% with dacarbazine (P = 0.05); median DOR was 6.5 months for trabectedin vs. 4.1 months for dacarbazine (P = 0.32). Grade 3/4 treatment-emergent adverse events observed in ≥ 10% of patients in the trabectedin group included transient aminotransferase (aspartate/alanine) elevations, anemia, leukopenia, and thrombocytopenia. Conclusions In this post hoc subset analysis of patients with uLMS who had received prior anthracycline therapy, trabectedin treatment resulted in significantly longer PFS versus dacarbazine, with an acceptable safety profile. There was no difference in OS.