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Efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with and without prior cytokine therapy, a subanalysis of TARGET

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Abstract

Before the development of targeted therapies, administration of cytokines (e.g., interleukin-2, interferon-α) was the primary systemic treatment option for advanced renal cell carcinoma. Sorafenib, an oral targeted, multikinase inhibitor, significantly prolonged progression-free survival and overall survival in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET), a large (N = 903) phase III, double-blind, randomised, placebo-controlled study of patients with advanced renal cell carcinoma resistant to standard therapy. This analysis of a patient subgroup from TARGET evaluated the safety and efficacy of sorafenib in patients who had received prior cytokine therapy (sorafenib: n = 374; placebo: n = 368) and in patients who were cytokine-naïve (sorafenib: n = 77; placebo: n = 84). Progression-free survival was significantly prolonged with sorafenib therapy compared with placebo among patients with and without prior cytokine therapy (respectively 5.5 vs. 2.7 months; hazard ratio, 0.54; 95% confidence interval, 0.45–0.64 and 5.8 vs. 2.8 months; hazard ratio, 0.48; 95% confidence interval, 0.32–0.73). Clinical benefit rates for sorafenib-treated patients compared with placebo patients were also higher (cytokine-treated: 83 vs. 54.3%; cytokine-naïve: 85.7 vs. 56.0%). Sorafenib was well tolerated in both subgroups (grade 3/4: 20 and 22%, respectively). Sorafenib demonstrated a consistent, significant clinical benefit against advanced renal cell carcinoma, with a twofold improvement in progression-free survival and disease control rate, with similar toxicities in patients with or without prior cytokine treatment.

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Authors and Affiliations

  1. Centre Leon Berard and Claude Bernard University, 28 Rue Laennec, Lyon, 69008, France

    S. Negrier

  2. Krankenhaus Nordwest, Frankfurt, Germany

    E. Jäger

  3. IRCCS San Matteo University Hospital Foundation, Pavia, Italy

    C. Porta

  4. Beth Israel Deaconess Medical Center, Boston, MA, USA

    D. McDermott

  5. Princess Margaret Hospital, Toronto, ON, Canada

    M. Moore

  6. University Hospital del Mar, Barcelona, Spain

    J. Bellmunt

  7. Bayer Pharmaceuticals, West Haven, CT, USA

    S. Anderson, F. Cihon & J. Lewis

  8. Institut Gustave Roussy, Villejuif, France

    B. Escudier

  9. Cleveland Clinic Cancer Center, Cleveland, OH, USA

    R. Bukowski

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  1. S. Negrier
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  2. E. Jäger
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  3. C. Porta
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  4. D. McDermott
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  5. M. Moore
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  8. F. Cihon
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  9. J. Lewis
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  10. B. Escudier
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Correspondence to S. Negrier.

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Negrier, S., Jäger, E., Porta, C. et al. Efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with and without prior cytokine therapy, a subanalysis of TARGET. Med Oncol 27, 899–906 (2010). https://doi.org/10.1007/s12032-009-9303-z

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  • DOI: https://doi.org/10.1007/s12032-009-9303-z

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