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  • Review Article
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Treatment selection in metastatic renal cell carcinoma: expert consensus

Nature Reviews Clinical Oncology volume 9, pages 327–337 (2012)Cite this article

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Abstract

In metastatic renal cell carcinoma (mRCC), many factors influence clinical decisions, including histology, tumour burden, prognostic factors, comorbidities, and the ability of the patient to tolerate treatment. Progression-free survival (PFS) durations reported from randomized trials of targeted therapies vary considerably, in part because of differences in patient characteristics. For first-line therapy, an estimate of PFS with sunitinib, bevacizumab plus interferon, or sorafenib in a 'general' population is 8–9 months, but each regimen is suitable for different patient categories. For example, sunitinib is suitable for all-prognosis groups, particularly younger, fitter patients; pazopanib for patients with a good or intermediate prognosis; bevacizumab plus interferon for good-prognosis patients or those with indolent disease; and sorafenib for patients at all prognostic risk levels, particularly the elderly and those with comorbidities. Sequential therapy with targeted agents provides significant benefit, and should be considered in all patients who can tolerate such treatment. Level 1 evidence supports sequential use of tyrosine kinase inhibitors, as well as these agents followed by everolimus. We consider how patient characteristics have influenced the results of studies of first-line therapy, and we provide expert opinion on the most appropriate treatment choices for particular patient groups receiving first-line and second-line therapy.

Key Points

  • Randomized trials of targeted therapies have shown a wide range of progression-free survival (PFS) durations, with more recent clinical trials often showing different results from early trials

  • Sunitinib, pazopanib, and bevacizumab plus interferon are suitable first-line therapies in patients with a good prognosis or intermediate prognosis; sorafenib is suitable for all-risk patients, those with comorbidities and the elderly

  • Following failure of first-line therapy, there are two valid options: sequencing of VEGF-targeted therapies or everolimus

  • VEGF-targeted therapies have distinct but overlapping targets, and sequential use targets successive escape pathways

  • Everolimus seems equally efficacious in patients who have already received one or two treatments with a tyrosine kinase inhibitor, suggesting that everolimus can be reserved for third line

  • Many studies (mostly retrospective) suggest that sorafenib followed by sunitinib provides improved cumulative PFS compared with sunitinib followed by sorafenib, and results of the SWITCH trial are awaited with interest

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Figure 1: Trials of targeted agents in first-line treatment.
Figure 2: Retrospective studies of sorafenib and sunitinib used in sequence.

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Acknowledgements

This Review was developed from a roundtable meeting on the occasion of the 2011 Sixth European International Kidney Cancer Symposium, Warsaw, Poland. The roundtable meeting was supported by an unrestricted grant by Bayer Healthcare, who had no input into the meeting or the Review. The authors thank Arthur Smyth Medina (Darwin Healthcare Communications) for editorial assistance.

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  1. Institut Gustave Roussy, 114 rue Edouard Vaillant, Villejuif, 94805, France

    Bernard Escudier

  2. Military Institute of Medicine and Health Services, 128 Szaserow Street, Warsaw, 00909, Poland

    Cezary Szczylik

  3. IRCCS San Matteo University Hospital Foundation, 19 Piazzale Golgi, Pavia, 27100, Italy

    Camillo Porta

  4. The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK

    Martin Gore

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Escudier, B., Szczylik, C., Porta, C. et al. Treatment selection in metastatic renal cell carcinoma: expert consensus. Nat Rev Clin Oncol 9, 327–337 (2012). https://doi.org/10.1038/nrclinonc.2012.59

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