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CHICAGO—Although the response rate (RR) was significantly improved, second-line treatment with amrubicin, a third-generation anthracycline and topoisomerase II inhibitor, missed the primary endpoint of significantly improving overall survival (OS) over topotecan in the Phase 3 open-label ACT-1 trial to treat small cell lung cancer (SCLC), according to results presented at the American Society of Clinical Oncology’s 2011 Annual Meeting. Patients receiving amrubicin had OS of 7.5 months compared with 7.8 months with topotecan (P=0.17). Robert Jotte, MD, of the Rocky Mountain Cancer Centers, Colorado, and colleagues observed that small numerical differences in patient characteristics in favor of the topotecan group may have affected OS.
The open-label, international trial enrolled 637 patients who were randomized 2:1 to amrubicin 40mg/m2 IV on Days 1–3 (n=424) or to topotecan 1.5mg/m2 IV on Days 1–5 (n=213), repeated every 3 weeks, with prophylactic white blood cell growth factors required in last third of the trial. Inclusion criteria were sensitive or refractory disease (progression ≥90 or <90 days after completion of first-line chemotherapy or response to first-line chemotherapy), one prior chemotherapy regimen, and ECOG PS 0–1.
In addition to OS, endpoints were response rate (RR; amrubicin 31.1%, topotecan 16.9%; P=0.0001), progression-free survival (PFS; amrubicin 4.1 months, topotecan 3.5 months; P=0.0182), time to progression (amrubicin 4.8 months, topotecan 4.2 months; P=0.009), and safety. Respective baseline characteristics were similar in the amrubicin and topotecan arms (median age: 62 vs. 61 years; patients <65: 60% vs. 65%; men: 58% vs. 60%; performance status of 0: 30% vs. 34%; refractory response to first-line platinum therapy: 47% vs. 45%). Survival trended in favor of amrubicin (hazard ratio [HR] 0.88), especially in the subgroup of refractory patients (HR 0.77; P=0.0469).
Grade 3 and 4 adverse events in amrubicin and topotecan groups, respectively, were: neutropenia (41% vs. 53%), thrombocytopenia (21% vs. 54%), anemia (16% vs. 30%), infections (13% vs. 9%), febrile neutropenia (10% vs. 4%; P<0.05 for all adverse event comparisons), and cardiac disorders (5% vs. 5%; P=.84). Due to concerns of cardiac toxicity with amrubicin, left ventricular ejection fraction (LVEF) was monitored throughout the study. It was observed that LVEF did not differ with cumulative doses of amrubicin compared with topotecan. Transfusion rates for amrubicin and topotecan were 32% and 53%, (P<.01).
Dr. Jotte concluded that although amrubicin did not improve OS, all secondary endpoints (RR, PFS, and enhanced symptom control) favored amrubicin. In the subset of refractory patients, however, an improvement in OS was observed.
