Randomized Phase Iii Trial Of Amrubicin Versus Topotecan (Topo) As Second-Line Treatment For Small Cell Lung Cancer (Sclc).

7000 Background: Amrubicin (AMR), a 3rd-generation anthracycline and potent topoisomerase II inhibitor, has shown promising activity in SCLC. The ACT-1 trial compared the safety and efficacy of AMR vs Topo for the 2nd-line treatment of SCLC. Methods: 637 patients (pts) were randomized 2:1 to AMR 40 mg/m2 IV on Day 1-3 (n=424) or to Topo 1.5 mg/m2 IV on Days 1-5 (n=213) with prophylactic WBC growth factors required in last 1/3 of trial. Endpoints were survival (OS, primary), response rate (RR), progression-free survival (PFS), and safety. Subgroup analyses used protocol-defined definitions: refractory pts had PD as best response to 1st-line therapy or progressed < 90 days. Results: Baseline characteristics were similar in the AMR vs Topo groups: median age 62 vs 61 years [yrs]; pts <65 yrs 60% vs 65%; men 58% vs 60%; performance status (PS) of 0 30% vs 34%; refractory 47% vs 45%. The covariates in the Cox model are PS of 0 (yes, no), age, response to 1st-line platinum-based therapy (refractory, sensitive), and disease stage (limited, extensive). Grade 3/4 adverse events in AMR and Topo groups, respectively, were: neutropenia (41% vs 53%), thrombocytopenia (21% vs 54%), anemia (16% vs 30%), infections (16% vs 10%), febrile neutropenia (10% vs 4%), all P<0.05, and cardiac disorders (5% vs 5%; P=0.84). Transfusion rates were 32% (AMR) and 53% (Topo), p<0.01. Conclusions: AMR is active in 2nd-line treatment of SCLC with significantly improved RR compared with Topo. Survival trended in favor of AMR (HR 0.88), especially in the subgroup of refractory patients (HR 0.77). Small numerical differences in pt characteristics in favor of the Topo group may have impacted OS. Quality of life data will be presented. N AMR Topo HR/OR 95% CI P value RR (%) 637 31 17 2.22 1.47-3.36 0.0002 PFS (mo) 637 4.1 4.0 0.999 0.84-1.19 0.98 OS (mo) 637 7.5 7.8 0.88 0.73-1.06 0.17 12-mo OS (%) 28 25 0.438 18-mo OS (%) 16 9 0.045 24-mo OS (%) 9 3 0.049 OS (Cox model) 637 - - 0.82 0.68-0.99 0.036 Subgroups OS sensitive pts (mo) 342 9.2 10 0.94 0.72-1.21 0.62 OS refractory pts (mo) 295 6.2 5.7 0.77 0.59-1.0 0.047 12-mo OS (%) 17 8 0.019 18-mo OS (%) 12 0 0.0006 Abbreviations: CI, confidence interval. Hazard ratio (HR) <1 and odds ratio (OR for RR only) > 1 favors AMR.