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Sequential therapy in metastatic renal cell carcinoma: pre-clinical and clinical rationale for selecting a second- or subsequent-line therapy with a different mechanism of action

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Abstract

Few types of cancer have had their treatment evolve as rapidly as metastatic renal cell carcinoma (mRCC). Since 2005, six new targeted therapies with proven efficacy have been approved for the treatment of mRCC. The downside is that our knowledge about the mechanisms of action of these therapies and the intrinsic and extrinsic mechanism of resistance has not evolved equally fast, and many questions remain unanswered. The only approved agent to date in the European Union for patients who progress on sunitinib or sorafenib is everolimus. The results of the phase III trial comparing axitinib vs. sorafenib after failure on sunitinib, bevacizumab, temsirolimus, or cytokines have recently been published, and axitinib has recently been licensed by the Food and Drugs Administration. Other phase III trials that are being conducted include a comparison between everolimus plus bevacizumab and everolimus after failure on tyrosine kinase inhibitors, and between temsirolimus and sorafenib after failure on sunitinib. In this article, we will review the available evidence from clinical studies on sequential therapy for mRCC, including those that are still in progress. In addition, information on the mechanism of resistance or tolerance to first-line therapy, recommendations of the main practice guidelines for second-line treatment, potential therapies for third or successive treatment lines, and the major reasons why patients who progress may benefit from a change of mechanism of action will also be discussed.

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Acknowledgments

The authors acknowledge the support of Novartis Oncology Spain, which has facilitated the necessary meetings to evaluate and discuss all the data presented in this review, and Dr. Ximena Alvira from HealthCo SL (Madrid, Spain) for assistance in the preparation of this manuscript.

Conflicts of interest

The authors declare that they do not have any conflict of interest that may inappropriately influence this work. J. Bellmunt has received honoraria and lectures fees from Novartis.

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Authors and Affiliations

  1. Hospital Clínico San Carlos, Madrid, Spain

    José Luís González Larriba & Javier Puente

  2. Hospital Universitario La Paz, Madrid, Spain

    Enrique Espinosa

  3. Complejo Hospitalario de Toledo, Toledo, Spain

    Icíar García Carbonero

  4. Hospital Universitario Fundación Alcorcón, Madrid, Spain

    Javier García-Donas

  5. Hospital Universitario Ramón y Cajal, Madrid, Spain

    María López

  6. Hospital General Universitario de Alicante, Alicante, Spain

    Andrés Meana

  7. Medical Oncology Service, Hospital Universitario del Mar-IMIM, Barcelona, Spain

    Joaquim Bellmunt

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  1. José Luís González Larriba
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  3. Icíar García Carbonero
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Correspondence to Joaquim Bellmunt.

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Larriba, J.L.G., Espinosa, E., Carbonero, I.G. et al. Sequential therapy in metastatic renal cell carcinoma: pre-clinical and clinical rationale for selecting a second- or subsequent-line therapy with a different mechanism of action. Cancer Metastasis Rev 31 (Suppl 1), 11–17 (2012). https://doi.org/10.1007/s10555-012-9354-z

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