A randomized phase III study of trabectedin (T) or dacarbazine (D) for the treatment of patients (pts) with advanced liposarcoma (LPS) or leiomyosarcoma (LMS).

Abstract

10503 Background: This phase III multicenter trial compared T with D in pts with advanced LPS or LMS previously treated with an anthracycline and at least one additional systemic therapy. Methods: Pts were randomized to T or D in a 2:1 ratio. Dosing of T and D were q 3 wks IV infusion: T (1.5 mg/m2 over 24 hr) vs D (1 g/m2 over 20-120 min). The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), time to progression (TTP), objective response rate (ORR), duration of response (DOR), symptom severity and safety. Cross-over to T after disease progression (PD) on D was not allowed until revision after this planned interim analysis (IA) of OS (50% events). The study is ongoing for final OS. Final results of secondary endpoints are presented. Results: The IA included 518 pts (T = 345, D = 173), 73% with LMS and 27% with LPS. Treatment with T resulted in a 45% reduction in the risk of PD or death compared with D (hazard ratio [HR] = 0.550; P < 0.0001; Median [M] 4.2 vs 1.5 months [mo], respectively), with benefit observed across all subgroups, and validated by independent radiologists audit. Other end points demonstrated improved efficacy of T: TTP (HR = 0.522, p < 0.0001; M = 4.2 vs 1.5 mo), clinical benefit rate (CR+PR+SD ≥ 18wks) (34.2% vs 18.5%; Odds Ratio[OR] = 2.291; p = 0.0002), ORR (9.9% vs 6.9%; OR = 1.467; p = 0.3269), DOR (HR=0.471, p = 0.1415; M = 6.5 vs 4.2 mo). The IA of OS (64% censored) demonstrated a 13% reduction in risk of death in T arm compared with D (HR = 0.872, p = 0.3741; M = 12.4 vs 12.9 mo). 34% of T and 17% of D pts received ≥ 6 cycles. The safety profiles were consistent with the well-characterized toxicities of both agents, with the most common grade 3-4 toxicities in T vs. D arm being ANC (40% vs 25%), platelets (19% vs 20%), increased ALT (29% vs 1%), and drug-related death (2.1% vs 0%). Patient-reported outcomes were similar across the arms, with low symptom scores during treatment. Conclusions: This phase III trial demonstrates improved disease control with T vs. D in advanced LPS and LMS, and confirms the acceptable benefit-risk profile of T from the prior randomized Phase 2 study (STS-201). T is a meaningful treatment option for pts with advanced LPS and LMS. Clinical trial information: NCT01343277.