Skip to main content

Advertisement

SpringerLink
Log in

Comprehensive overview of the efficacy and safety of sorafenib in advanced or metastatic renal cell carcinoma after a first tyrosine kinase inhibitor

  • Educational Series – Red Series
  • New Trends in Clinical Oncology
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 04 April 2013

Abstract

We performed a literature search that shed light on the signaling pathways involved in the sorafenib activity as first- or subsequent-line treatment, taking into account its toxicity profile. Sorafenib appears to have better tolerability when compared with other agents in the same indication. Cross-resistance between tyrosine kinase inhibitors (TKIs) may be limited, even after failure with a previous VEGFR inhibitor, but the optimal sequence with TKIs remains to be determined. Randomized trials of second-line treatment options have showed either modest or no differences in terms of progression-free and overall survival (OS). Direct comparison between sorafenib and axitinib demonstrated differences in terms of PFS in favor of axitinib, but not in terms of OS as second-line treatment. In contrast, a phase III study showed a benefit in OS, favoring sorafenib when compared with temsirolimus. In conclusion, after using other VEGF inhibitor such as sunitinib, sorafenib is active and safe for the treatment of patients with advanced or metastatic RCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Motzer RJ, Hutson TE, Tomczak P et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590

    Article  PubMed  CAS  Google Scholar 

  2. Escudier B, Eisen T, Stadler WM et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134

    Article  PubMed  CAS  Google Scholar 

  3. Escudier B, Eisen T, Stadler WM 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. J Clin Oncol 27:3312–3318

    Article  PubMed  CAS  Google Scholar 

  4. Bellmunt J, Guix M (2009) The medical management of metastatic renal cell carcinoma: integrating new guidelines and recommendations. BJU Int 103:572–577

    Article  PubMed  CAS  Google Scholar 

  5. Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124

    Article  PubMed  CAS  Google Scholar 

  6. Calvo E, Escudier B, Motzer RJ et al (2012) Everolimus in metastatic renal cell carcinoma: subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer 48:333–339

    Article  PubMed  CAS  Google Scholar 

  7. Motzer RJ, 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  PubMed  CAS  Google Scholar 

  8. Motzer RJ, Escudier B, Oudard S et al (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116:4256–4265

    Article  PubMed  CAS  Google Scholar 

  9. U.S. Food and Drug Administration (U.S. FDA). INLYTA(R) (Axitinib). http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM283657.pdf. Access date: 1 July 2012

  10. Rini BI, Escudier B, Tomczak P et al (2011) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378:1931–1939

    Article  PubMed  CAS  Google Scholar 

  11. Lowy DR, Willumsen BM (1993) Function and regulation of Ras. Annu Rev Biochem 62:851–891

    Article  PubMed  CAS  Google Scholar 

  12. Bos JL (1989) Ras oncogenes in human cancer: a review. Cancer Res 49:4682–4689

    PubMed  CAS  Google Scholar 

  13. Naumann U, Eisenmann-Tappe I, Rapp UR (1997) The role of Raf kinases in development and growth of tumors. Recent Results Cancer Res 143:237–244

    Article  PubMed  CAS  Google Scholar 

  14. Chong H, Lee J, Guan KL (2001) Positive and negative regulation of Raf kinase activity and function by phosphorylation. EMBO J 20:3716–3727

    Article  PubMed  CAS  Google Scholar 

  15. Malumbres M, Barbacid M (2003) RAS oncogenes: the first 30 years. Nat Rev Cancer 3:459–465

    Article  PubMed  CAS  Google Scholar 

  16. Davies H, Bignell GR, Cox C et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954

    Article  PubMed  CAS  Google Scholar 

  17. Rajagopalan H, Bardelli A, Lengauer C et al (2002) Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418:934

    Article  PubMed  CAS  Google Scholar 

  18. Wilhelm SM, Carter C, Tang L et al (2004) BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109

    Article  PubMed  CAS  Google Scholar 

  19. Wilhelm S, Housley T, Kennure N (2001) A novel diphenylurea Raf kinase inhibitor (RKI) blocks the Raf/MEK/ERK pathway in tumor cells. Proc Am Assoc Cancer Res 42:923

    Google Scholar 

  20. Wilhelm S, Chien DS (2002) BAY 43–9006: preclinical data. Curr Pharm Des 8:2255–2257

    Article  PubMed  CAS  Google Scholar 

  21. Folkman J (1992) The role of angiogenesis in tumor growth. Semin Cancer Biol 3:65–71

    PubMed  CAS  Google Scholar 

  22. Na X, Wu G, Ryan CK et al (2003) Overproduction of vascular endothelial growth factor related to von Hippel–Lindau tumor suppressor gene mutations and hypoxia-inducible factor-1 alpha expression in renal cell carcinomas. J Urol 170:588–592

    Article  PubMed  CAS  Google Scholar 

  23. Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2:727–739

    Article  PubMed  CAS  Google Scholar 

  24. Lyons JF, Wilhelm S, Hibner B et al (2001) Discovery of a novel Raf kinase inhibitor. Endocr Relat Cancer 8:219–225

    Article  PubMed  CAS  Google Scholar 

  25. Strumberg D, Richly H, Hilger RA et al (2005) Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43–9006 in patients with advanced refractory solid tumors. J Clin Oncol 23:965–972

    Article  PubMed  CAS  Google Scholar 

  26. Moore M, Hirte HW, Siu L et al (2005) Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43–9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol 16:1688–1694

    Article  PubMed  CAS  Google Scholar 

  27. Clark JW, Eder JP, Ryan D et al (2005) Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43–9006, in patients with advanced, refractory solid tumors. Clin Cancer Res 11:5472–5480

    Article  PubMed  CAS  Google Scholar 

  28. Negrier S, Jager E, Porta C et al (2010) 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

    Article  PubMed  CAS  Google Scholar 

  29. Stadler WM, Figlin RA, McDermott DF et al (2010) Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 116:1272–1280

    Article  PubMed  CAS  Google Scholar 

  30. Beck J, Procopio G, Bajetta E et al (2011) Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann Oncol 22:1812–1823

    Article  PubMed  CAS  Google Scholar 

  31. Dudek AZ, Zolnierek J, Dham A et al (2009) Sequential therapy with sorafenib and sunitinib in renal cell carcinoma. Cancer 115:61–67

    Article  PubMed  CAS  Google Scholar 

  32. Sablin MP, Negrier S, Ravaud A et al (2009) Sequential sorafenib and sunitinib for renal cell carcinoma. J Urol 182:29–34; discussion 34

    Google Scholar 

  33. Vickers MM, Choueiri TK, Rogers M et al (2010) Clinical outcome in metastatic renal cell carcinoma patients after failure of initial vascular endothelial growth factor-targeted therapy. Urology 76:430–434

    Article  PubMed  Google Scholar 

  34. Porta C, Procopio G, Carteni G et al (2011) Sequential use of sorafenib and sunitinib in advanced renal-cell carcinoma (RCC): an Italian multicentre retrospective analysis of 189 patient cases. BJU Int 108:E250–E257

    Article  PubMed  Google Scholar 

  35. Heng DYC, Lee J-L, Harshman LC et al (2012) A population-based overview of sequences of targeted therapy in metastatic renal cell carcinoma (mRCC). ASCO Meeting Abstracts 30:387

    Google Scholar 

  36. Kontovinis L, Laschos K, Karadimou A et al (2012) Sequential treatment with sorafenib and sunitinib in metastatic renal cell carcinoma: clinical outcomes from a retrospective clinical study. Med Oncol 29:750–754

    Article  PubMed  CAS  Google Scholar 

  37. Rini BI, Escudier BJ, Michaelson MD et al (2012) Phase III AXIS trial for second-line metastatic renal cell carcinoma (mRCC): effect of prior first-line treatment duration and axitinib dose titration on axitinib efficacy. ASCO Meeting Abstracts 30:354

    Google Scholar 

  38. Gore ME, Jones RJ, Ravaud A et al (2011) Efficacy and safety of intrapatient dose escalation of sorafenib as first-line treatment for metastatic renal cell carcinoma (mRCC). ASCO Meeting Abstracts 29:4609

    Google Scholar 

  39. Hutson TE, Escudier B, Esteban E et al (2012) Temsirolimus vs. sorafenib as second line therapy in metastatic renal cell carcinoma: results from the INTORSECT trial. Ann Oncol 23(suppl 9):IXE14

    Google Scholar 

  40. Michel MS, Vervenne W, Goebell PJ et al (2012) Phase III randomized sequential open-label study to evaluate efficacy and safety of sorafenib (SO) followed by sunitinib (SU) versus sunitinib followed by sorafenib in patients with advanced/metastatic renal cell carcinoma without prior systemic therapy (SWITCH Study): safety interim analysis results. ASCO Meeting Abstracts 30:4539

    Google Scholar 

  41. Garcia JA, Hutson TE, Elson P et al (2010) Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab. Cancer 116:5383–5390

    Article  PubMed  CAS  Google Scholar 

  42. Sabbatini R, Porta C, Procopio G (2009) Use of tyrosine kinase inhibitors (TKI) in hemodialitic metastatic renal cell carcinoma patients. Eur Urol 8:185 (Abstract 258)

    Google Scholar 

  43. Calvani N, Morelli F, Leo S et al (2012) Sequential use of sorafenib and sunitinib in advanced renal cell carcinoma: does the order of sequencing matter? Med Oncol 29(3):1908–1913

    Google Scholar 

  44. Protzel C, Ruppin S, Klebingat KJ et al (2008) Sorafenib for the treatment of metastatic renal cell carcinoma with chronic renal failure. Onkologie 31(Supp 1):PE591

    Google Scholar 

  45. Maroto P, Villavicencio H (2008) Sorafenib: tolerance in Patients on Chronic Hemodialysis. Oncology 74:245–246

    Article  Google Scholar 

  46. Hilger RA, Richly H, Grubert M et al (2009) Pharmacokinetics of sorafenib in patients with renal impairment undergoing hemodialysis. Int J Clin Pharmacol Ther 47:61–64

    PubMed  CAS  Google Scholar 

  47. Ruppin S, Protzel C, Klebingat KJ et al (2009) Successful sorafenib treatment for metastatic renal cell carcinoma in a case with chronic renal failure. Eur Urol 55:986–988; quiz 988

    Google Scholar 

  48. Bellmunt J, Eisen T, Fishman M et al (2011) Experience with sorafenib and adverse event management. Crit Rev Oncol Hematol 78:24–32

    Article  PubMed  Google Scholar 

  49. Szczylik C, Cella D, Eisen T et al (2008) Comparison of kidney cancer symptoms and quality of life (QoL) in renal cell cancer (RCC) patients (pts) receiving sorafenib vs interferon-{alpha} (IFN). ASCO Meeting Abstracts 26:9603

    Google Scholar 

Download references

Acknowledgments

The authors acknowledge the editorial assistance of Fernando Sánchez Barbero from HealthCo SL (Madrid, Spain), which was founded by Bayer Hispania.

Conflict of interest

The authors declare that they have no conflict of interest relating to the publication of this manuscript.

Author information

Authors and Affiliations

  1. Complexo Hospitalario Arquitecto Marcide, Ferrol, Spain

    F. J. Afonso

  2. Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain

    U. Anido & L. León

  3. Complexo Hospitalario Universitario de Ourense, Ourense, Spain

    O. Fernández-Calvo

  4. Hospital Universitario Lucus Augustí, Lugo, Spain

    S. Vázquez-Estévez

  5. Complexo Hospitalario Universitario, Vigo, Spain

    M. Lázaro

  6. Centro Oncológico de Galica, A Coruña, Spain

    M. Ramos

  7. Medical Oncology Service, Complexo Hospitalario Universitario A Coruña, 84 As Xubias, 15006, A Coruña, Spain

    L. Antón-Aparicio

Authors
  1. F. J. Afonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U. Anido
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. Fernández-Calvo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Vázquez-Estévez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. León
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Lázaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Ramos
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L. Antón-Aparicio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Antón-Aparicio.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Afonso, F.J., Anido, U., Fernández-Calvo, O. et al. Comprehensive overview of the efficacy and safety of sorafenib in advanced or metastatic renal cell carcinoma after a first tyrosine kinase inhibitor. Clin Transl Oncol 15, 425–433 (2013). https://doi.org/10.1007/s12094-012-0985-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-012-0985-x

Keywords

Search

Navigation