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Updated recommendations from the Spanish Oncology Genitourinary Group on the treatment of advanced renal cell carcinoma

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Abstract

The speed at which targeted therapies are being developed and incorporated into the treatment of advanced renal cell carcinoma (RCC) is surprising. After decades in which the only systemic treatment options available for advanced disease were interleukin-2 and interferon-α, in the last decade, six new targeted therapies have emerged showing meaningful clinical benefits to patients with advanced RCC through phase III trials. Recently, the Spanish Oncology Genitourinary Group issued its first public statement of recommendations for the optimal management of advanced RCC. However, most pivotal phase III trials on which these recommendations were based have been updated and/or fully reported. Moreover, a new multikinase inhibitor, pazopanib, has emerged with good quality clinical data. In this report, we review in depth the latest phase III data of targeted therapies for advanced RCC and update our recommendations. Furthermore, we hypothesize about the best environment for patients with advanced RCC to receive cancer therapy.

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References

  1. Jemal, A., Siegel, R., Ward, E., et al. (2009). Cancer statistics, 2009. CA: A Cancer Journal for Clinicians, 59, 225–249.

    Article  Google Scholar 

  2. Bellmunt, J., Calvo, E., Castellano, D., et al. (2009). Recommendations from the Spanish Oncology Genitourinary Group for the treatment of metastatic renal cancer. Cancer Chemotherapy and Pharmacology, 63(Suppl 1), S1–S13.

    Article  PubMed  Google Scholar 

  3. Amato, R. J. (2000). Chemotherapy for renal cell carcinoma. Seminars in Oncology, 27, 177–186.

    CAS  PubMed  Google Scholar 

  4. Lam, J. S., Leppert, J. T., Figlin, R. A., et al. (2005). Surveillance following radical or partial nephrectomy for renal cell carcinoma. Current Urology Reports, 6, 7–18.

    Article  PubMed  Google Scholar 

  5. Bukowski, R. M. (2009). Prognostic factors for survival in metastatic renal cell carcinoma: update 2008. Cancer, 115, 2273–2281.

    Article  CAS  PubMed  Google Scholar 

  6. Lughezzani, G., Capitanio, U., Jeldres, C., et al. (2009). Prognostic significance of lymph node invasion in patients with metastatic renal cell carcinoma: a population-based perspective. Cancer, 115, 5680–5687.

    Article  PubMed  Google Scholar 

  7. Ljungberg, B., Landberg, G., & Alamdari, F. I. (2000). Factors of importance for prediction of survival in patients with metastatic renal cell carcinoma, treated with or without nephrectomy. Scandinavian Journal of Urology and Nephrology, 34, 246–251.

    Article  CAS  PubMed  Google Scholar 

  8. Atkins, M. B., Ernstoff, M. S., Figlin, R. A., et al. (2007). Innovations and challenges in renal cell carcinoma: summary statement from the Second Cambridge Conference. Clinical Cancer Research, 13, 667s–670s.

    Article  PubMed  Google Scholar 

  9. Tunuguntla, H. S., & Jorda, M. (2008). Diagnostic and prognostic molecular markers in renal cell carcinoma. Journal d'Urologie, 179, 2096–2102.

    Article  CAS  Google Scholar 

  10. Escudier, B., Eisen, T., Stadler, W. M., et al. (2009). Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. Journal of Clinical Oncology, 27, 3312–3318.

    Article  CAS  PubMed  Google Scholar 

  11. Heng, D. Y., Xie, W., Regan, M. M., et al. (2009). Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. Journal of Clinical Oncology, 27, 5794–5799.

    Article  CAS  PubMed  Google Scholar 

  12. Klatte, T., Rao, P. N., de Martino, M., et al. (2009). Cytogenetic profile predicts prognosis of patients with clear cell renal cell carcinoma. Journal of Clinical Oncology, 27, 746–753.

    Article  PubMed  Google Scholar 

  13. Motzer, R. J., Michaelson, M. D., Redman, B. G., et al. (2006). Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology, 24, 16–24.

    Article  CAS  PubMed  Google Scholar 

  14. Motzer, R. J., Rini, B. I., Bukowski, R. M., et al. (2006). Sunitinib in patients with metastatic renal cell carcinoma. Jama, 295, 2516–2524.

    Article  CAS  PubMed  Google Scholar 

  15. Figlin, R. A., Hutson, T. E., Tomczak, P., et al (2008). Overall survival with sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC). Chicago: ASCO Annual Meeting

  16. Motzer, R. J., Hutson, T. E., Tomczak, P., et al. (2007). Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. The New England Journal of Medicine, 356, 115–124.

    Article  CAS  PubMed  Google Scholar 

  17. Motzer, R. J., Hutson, T. E., Tomczak, P., et al. (2009). Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology, 27, 3584–3590.

    Article  CAS  PubMed  Google Scholar 

  18. Cella, D., Li, J. Z., Cappelleri, J. C., et al. (2008). Quality of life in patients with metastatic renal cell carcinoma treated with sunitinib or interferon alfa: results from a phase III randomized trial. Journal of Clinical Oncology, 26, 3763–3769.

    Article  CAS  PubMed  Google Scholar 

  19. Choueiri, T. K., & Bellmunt, J. (2009). Sunitinib in renal-cell carcinoma: expanded indications. The Lancet Oncology, 10, 740.

    Article  PubMed  Google Scholar 

  20. Gore, M. E., Szczylik, C., Porta, C., et al. (2009). Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. The Lancet Oncology, 10, 757–763.

    Article  CAS  PubMed  Google Scholar 

  21. EMEA. (2009). Sunitinib (Sutent®)—summary of product characteristics. http://www.ema.europa.eu/humandocs/PDFs/EPAR/sutent/emea-combined-h687en.pdf.

  22. FDA. (2007). Sunitinib (Sutent®)—full prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021968s002s003s004s005s006lbl.pdf.

  23. Akaza, H., Tsukamoto, T., Murai, M., et al. (2007). Phase II study to investigate the efficacy, safety, and pharmacokinetics of sorafenib in Japanese patients with advanced renal cell carcinoma. Japanese Journal of Clinical Oncology, 37, 755–762.

    Article  PubMed  Google Scholar 

  24. Escudier, B., Eisen, T., Stadler, W. M., et al. (2007). Sorafenib in advanced clear-cell renal-cell carcinoma. The New England Journal of Medicine, 356, 125–134.

    Article  CAS  PubMed  Google Scholar 

  25. Escudier, B., Szczylik, C., Hutson, T. E., et al. (2009). Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology, 27, 1280–1289.

    Article  CAS  PubMed  Google Scholar 

  26. EMEA. (2009). Sorafenib (Nexavar®)—summary of product characteristics. http://www.ema.europa.eu/humandocs/PDFs/EPAR/nexavar/emea-combined-h690en.pdf.

  27. FDA. (2007). Sorafenib (Nexavar®)—full prescribing information: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021923s004s005s006s007lbl.pdf.

  28. Bukowski, R. M., Yasothan, U., & Kirkpatrick, P. (2010). Pazopanib. Nature Reviews Drug Discovery, 9, 17–18.

    Article  CAS  PubMed  Google Scholar 

  29. Sternberg, C. N., Davis, I. D., Mardiak, J., et al. (2010). Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. Journal of Clinical Oncology, 28, 1061–1068.

    Article  CAS  PubMed  Google Scholar 

  30. Hawkins, R. E., Hong, S. J., Ulys, A., et al. (2009). An open-label extension study to evaluate safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Journal of clinical oncology (Meeting Abstracts), 27, 5110.

    Google Scholar 

  31. FDA. (2009). Pazopanib (Votrient®)—full prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf.

  32. Dvorak, H. F. (2002). Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. Journal of Clinical Oncology, 20, 4368–4380.

    Article  CAS  PubMed  Google Scholar 

  33. Escudier, B., Pluzanska, A., Koralewski, P., et al. (2007). Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet, 370, 2103–2111.

    Article  PubMed  Google Scholar 

  34. Rini, B. I., Halabi, S., Rosenberg, J. E., et al. (2008). CALGB 90206: a phase III trial of bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in metastatic renal cell carcinoma. San Francisco: Genitourinary Cancers Symposium

  35. Escudier, B. J., Bellmunt, J., Negrier, S., et al. (2009). Final results of the phase III, randomized, double-blind AVOREN trial of first-line bevacizumab (BEV) + interferon-{alpha}2a (IFN) in metastatic renal cell carcinoma (mRCC). Journal of Clinical Oncology (Meeting Abstracts), 27, 5020.

    Google Scholar 

  36. Rini, B. I., Halabi, S., Rosenberg, J., et al. (2009). Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in patients with metastatic renal cell carcinoma: results of overall survival for CALGB 90206. Journal of Clinical Oncology (Meeting Abstracts), 27, LBA5019.

    Google Scholar 

  37. EMEA. (2009). Bevacizumab (Avastin®)—summary of product characteristics. http://www.ema.europa.eu/humandocs/PDFs/EPAR/avastin/emea-combined-h582en.pdf.

  38. FDA. (2009). Bevacizumab (Avastin®)—full prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125085s0168lbl.pdf.

  39. Hudes, G., Carducci, M., Tomczak, P., et al. (2007). Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. The New England Journal of Medicine, 356, 2271–2281.

    Article  CAS  PubMed  Google Scholar 

  40. Parasuraman, S., Hudes, G., Levy, D., et al. (2007). Comparison of quality-adjusted survival in patients with advanced renal cell carcinoma receiving first-line treatment with temsirolimus (TEMSR) or interferon-{alpha} (IFN) or the combination of IFN + TEMSR. Journal of Clinical Oncology (Meeting Abstracts), 25, 5049.

    Google Scholar 

  41. EMEA. (2009). Temsirolimus (Torisel®)—summary of product characteristics. http://www.ema.europa.eu/humandocs/PDFs/EPAR/torisel/emea-combined-h799en.pdf.

  42. FDA. (2007). Temsirolimus (Torisel®)—full prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022088lbl.pdf.

  43. Motzer, R. J., Escudier, B., Oudard, S., et al. (2008). Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet, 372, 449–456.

    Article  CAS  PubMed  Google Scholar 

  44. Wiederkehr, D., Howe, C. J., Casciano, R., et al. (2009). Overall survival among metastatic renal cell carcinoma patients corrected for crossover using inverse probability of censoring weights: analyses from the everolimus phase III trial. European Journal of Cancer Supplements, 7, 432.

    Article  Google Scholar 

  45. EMEA. (2009). Everolimus (Afinitor®)—summary of product characteristics. http://www.ema.europa.eu/humandocs/PDFs/EPAR/afinitor/emea-combined-h1038en.pdf.

  46. FDA. (2009). Everolimus (Afinitor®)—full prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022334lbl.pdf.

  47. Pantuck, A. J., Seligson, D. B., Klatte, T., et al. (2007). Prognostic relevance of the mTOR pathway in renal cell carcinoma: implications for molecular patient selection for targeted therapy. Cancer, 109, 2257–2267.

    Article  CAS  PubMed  Google Scholar 

  48. Thompson, R. H., Zang, X., Lohse, C. M., et al. (2008). Evaluation of soluble B7x as a serum marker in patients with clear cell renal cell carcinoma. Journal of Clinical Oncology (Meeting Abstracts), 26, 5052.

    Google Scholar 

  49. Bui, M. H., Seligson, D., Han, K. R., et al. (2003). Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. Clinical Cancer Research, 9, 802–811.

    CAS  PubMed  Google Scholar 

  50. Patard, J. J., Fergelot, P., Karakiewicz, P. I., et al. (2008). Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma. International Journal of Cancer, 123, 395–400.

    Article  CAS  Google Scholar 

  51. Kim, H., Yi, S., Jun, H., et al. (2008). Use of biomakers to predict outcomes of immunotherapy for metastatic renal cell carcinoma. Journal of Clinical Oncolog (Meeting Abstracts), 26, 16015.

    Google Scholar 

  52. Tanimoto, S., Fukumori, T., El-Moula, G., et al. (2008). Prognostic significance of serum hepatocyte growth factor in clear cell renal cell carcinoma: comparison with serum vascular endothelial growth factor. The Journal of Medical Investigation, 55, 106–111.

    Article  PubMed  Google Scholar 

  53. Klatte, T., Seligson, D. B., Riggs, S. B., et al. (2007). Hypoxia-inducible factor 1 alpha in clear cell renal cell carcinoma. Clinical Cancer Research, 13, 7388–7393.

    Article  CAS  PubMed  Google Scholar 

  54. Bui, M. H., Visapaa, H., Seligson, D., et al. (2004). Prognostic value of carbonic anhydrase IX and KI67 as predictors of survival for renal clear cell carcinoma. Journal d'Urologie, 171, 2461–2466.

    Article  Google Scholar 

  55. Weiss, R. H., Borowsky, A. D., Seligson, D., et al. (2007). p21 is a prognostic marker for renal cell carcinoma: implications for novel therapeutic approaches. Journal d'Urologie, 177, 63–68. discussion 68-9.

    Article  CAS  Google Scholar 

  56. Kim, H. L., Seligson, D., Liu, X., et al. (2005). Using tumor markers to predict the survival of patients with metastatic renal cell carcinoma. Journal d'Urologie, 173, 1496–1501.

    Article  CAS  Google Scholar 

  57. Shvarts, O., Seligson, D., Lam, J., et al. (2005). p53 is an independent predictor of tumor recurrence and progression after nephrectomy in patients with localized renal cell carcinoma. Journal d'Urologie, 173, 725–728.

    Article  CAS  Google Scholar 

  58. Bukowski, R. M., Eisen, T., Szczylik, C., et al. (2007). Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: survival and biomarker analysis. Journal of Clinical Oncology (Meeting Abstracts), 25, 5023.

    Google Scholar 

  59. Patel, P. H., Chadalavada, R. S., Ishill, N. M., et al. (2008). Hypoxia-inducible factor (HIF) 1{alpha} and 2{alpha} levels in cell lines and human tumor predicts response to sunitinib in renal cell carcinoma (RCC). Journal of Clinical Oncology (Meeting Abstracts), 26, 5008.

    Google Scholar 

  60. Jaeger, E., Waldman, F., Roydasgupta, R., et al. (2008). Array-based comparative genomic hybridization (CGH) identifies chromosomal imbalances between Interleukin-2 complete and non-responders. Journal of Clinical Oncology (Meeting Abstracts), 26, 5043.

    Google Scholar 

  61. Faber, P. W., Vaziri, S. A., Wood, L., et al. (2008). Potential non-synonymous single nucleotide polymorphisms (nsSNPs) associated with toxicity in metastatic clear cell renal cell carcinoma (MCCRCC) patients (pts) treated with sunitinib. Journal of Clinical Oncology (Meeting Abstracts), 26, 5009.

    Google Scholar 

  62. Choueiri, T. K., Vaziri, S. A., Jaeger, E., et al. (2008). von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma. Journal d'Urologie, 180, 860–865. discussion 865-6.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge the support of Novartis Farmacéutica, which facilitated the necessary meetings to evaluate and discuss all the data presented in this review, and Dr. Beatriz Gil-Alberdi from HealthCo SL (Madrid, Spain) for her assistance in the preparation of this manuscript.

Conflict of Interest

E. Calvo has received consulting fees from Roche, Pfizer, Novartis. He has received honoraria from Roche, Pfizer, Novartis. He has received research funding from Roche, Pfizer, Novartis. P. Maroto has received consulting fees from Wyeth, Pfizer. He has received honoraria from Wyeth, Roche, Pfizer, Bayer. X. Garcia del Muro has no conflict of interest. M. A. Climent has received consulting fees from Bayer, GSK, Pfizer, Novartis. He has received honoraria from Wyeth. J. L. González-Larriba has no conflict of interest. E. Esteban has no conflict of interest. R. Lopez has received consulting fees from Novartis, Roche, GSK. He has received research funding from Novartis. L. Paz-Ares has honoraria from Pfizer, Novartis. J. Bellmunt has received consulting fees from Bayer, Roche, Pfizer, Novartis. D. Castellano has no conflict of interest.

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Authors and Affiliations

  1. Hospital de Madrid-CIOCC, Madrid, Spain

    Emiliano Calvo

  2. Hospital de la Santa Creu i San Pau, Barcelona, Spain

    Pablo Maroto

  3. Institut Català d’Oncologia, Barcelona, Spain

    Xavier García del Muro

  4. Instituto Valenciano de Oncología, Valencia, Spain

    Miguel Ángel Climent

  5. Hospital Clínico San Carlos, Madrid, Spain

    José Luis González-Larriba

  6. Hospital Universitario Central de Asturias, Oviedo, Spain

    Emilio Esteban

  7. Complexo Hospitalario Universitario de Santiago, A Coruña, Spain

    Rafael López

  8. Hospital Virgen del Rocío, Sevilla, Spain

    Luis Paz-Ares

  9. Hospital del Mar, Barcelona, Spain

    Joaquim Bellmunt

  10. Medical Oncology Service, Hospital Universitario 12 de Octubre, Avda. De Córdoba, s/n, 28041, Madrid, Spain

    Daniel Castellano

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  1. Emiliano Calvo
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Correspondence to Daniel Castellano.

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Calvo, E., Maroto, P., del Muro, X.G. et al. Updated recommendations from the Spanish Oncology Genitourinary Group on the treatment of advanced renal cell carcinoma. Cancer Metastasis Rev 29 (Suppl 1), 1–10 (2010). https://doi.org/10.1007/s10555-010-9231-6

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