Randomized phase 3 trial of amrubicin versus topotecan as second-line treatment for small cell lung cancer (SCLC)

Introduction: Amrubicin (AMR), a 3rd generation anthracycline and topoisomeraseII inhibitor, has shown promising activity in SCLC. The ACT-1 trialcompared the safety and efficacy of AMR with topotecan (Topo) for secondlinetreatment of SCLC.Methods: Patients with SCLC received either AMR 40mg/m2 IV on day 1-3(n=424) or Topo 1.5mg/m2 IV on days 1-5 (n=213) with prophylactic WBCgrowth factors and antibiotics required in last 1/3 of trial. Study endpointsincluded overall survival (OS), response rate (RR), progression-free survival(PFS), and safety. Subgroup analyses used protocol-defined definitions:refractory patients had PD as best response to first-line therapy or progressed<90 days. The mean change in Lung Cancer Symptom Scale (LCSS), Symptom Burden (LCSS SB) score, and EQ - 5D were used to assess qualityof life (QoL).Results: Both the AMR and Topo groups had similar baseline characteristics:median age 62 vs 61 years; patients <65 years 60% vs 65%; men 58% vs60%; performance status 0 30% vs 34%; refractory 47% vs 45%.The Cox model covariates were PS 0 (yes, no), age, response to first-lineplatinum-based therapy (refractory, sensitive), and disease stage (limited, extensive). AMR treated patients had better symptom control and QoL thanTopo treated patients: LCSS 0.2 vs 5.6, and LCSS-SB-0.1 vs 5.2 for AMR andTopo, respectively, all P<0.05. The respective grade 3/4 adverse events inAMR and Topo groups 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).Conclusions: AMR showed clinical efficacy in second-line treatment ofSCLC, and significantly improved RR and PFS compared with Topo. The OStrended in favor of AMR (HR 0.88), especially in refractory patients (HR0.77). Preliminary QoL results favored AMR. (Figure presented).