Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer [JCO article]

Joachim von Pawel, Robert Jotte, David R Spigel, Mary E R O'Brien, Mark A Socinski, Jörg Mezger, Martin Steins, Léon Bosquée, Jeffrey Bubis, Kristiaan Nackaerts, José M Trigo, Philip Clingan, Wolfgang Schütte, Paul Lorigan, Martin Reck, Manuel Domine, Frances A Shepherd, Shaoyi Li, Markus F Renschler

    Research output: Contribution to journalArticlepeer-review


    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. 
    CONCLUSION: Amrubicin did not improve survival when compared with topotecan in the second-line treatment of patients with SCLC. OS did not differ significantly between treatment groups, although an improvement in OS was noted in patients with refractory disease treated with amrubicin.
    Original languageEnglish
    Pages (from-to)4012-4019
    Number of pages8
    JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
    Issue number35
    Publication statusPublished - 10 Nov 2014


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