Randomized Phase III Trial of Amrubicin Versus Topotecan As Second-Line Treatment for Patients With Small-Cell Lung Cancer

作者：Joachim von Pawel, Robert M. Jotte, David Robert Spigel, Mary E.R. O'Brien, Mark A. Socinski, Jörg Michael Mezger, Martin B. Steins, Leon Bosquée, Jeffrey Alan Bubis, Kristiaan Nackaerts, José Manuel Trigo, Philip Clingan, Wolfgang Schütte, Paul C. Lorigan, Martin Reck, Manuel Dómine, Frances Alice Shepherd, Shaoyi Li, Markus Frederic Renschler · 发表于：Journal of Clinical Oncology · 年份：2014 · DOI：10.1200/jco.2013.54.5392 · 被引用次数：350 · 研究领域：Lung Cancer Research Studies、Cancer therapeutics and mechanisms、Lung Cancer Treatments and Mutations

PURPOSE: Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II trials. This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC. PATIENTS AND METHODS: A total of 637 patients with refractory or sensitive SCLC were randomly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m(2) intravenously (IV) on days 1 to 3 or topotecan 1.5 mg/m(2) IV on days 1 to 5. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival (PFS), and safety. RESULTS: Median OS was 7.5 months with amrubicin versus 7.8 months with topotecan (hazard ratio [HR], 0.880; P = .170); in refractory patients, median OS was 6.2 and 5.7 months, respectively (HR, 0.77; P = .047). Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan (HR, 0.802; P = .018). ORR was 31.1% with amrubicin and 16.9% with topotecan (odds ratio, 2.223; P < .001). Grade ≥ 3 treatment-emergent adverse events in the amrubicin and topotecan arms were: neutropenia (41% v 54%; P = .004), thrombocytopenia (21% v 54%; P < .001), anemia (16% v 31%; P < .001), infections (16% v 10%; P = .043), febrile neutropenia (10% v 3%; P = .003), and cardiac disorders (5% v 5%; P = .759); transfusion rates were 32% and 53% (P < .001), respectively. NQO1 polymorphisms did not influence safety outcomes. CONC...