Treatment Efficacy of Targeted Therapies for Metastatic Renal Cell Carcinoma—A Review after Seven Years of Experience
Affiliation(s)
Department of Oncology, Siloah Hospital, Hannover, Germany. Department of Urology, RWTH Aachen University, Aachen, Germany.
Department of Oncology, Siloah Hospital, Hannover, Germany. Department of Urology, RWTH Aachen University, Aachen, Germany.
ABSTRACT
Renal cell carcinoma (RCC) is the 10th leading cause of deaths from cancer in the Western world. During the last two decades this type of malignancy was difficult to treat with limited treatment options using cytokines like interferon alpha (IFN) or interleukin-2 (IL-2). The development of targeted therapies that interfere with specific pathways of tumor angiogenesis and proliferation has profoundly changed this situation and improved the prognosis for patients diagnosed with metasatic renal cellcarcinoma (mRCC) considerably. To date, seven targeted therapies have been approved for the first- and second-line treatment of metastatic renal cell carcinoma. In addition, recent data suggest that sequential treatment with these modern drugs is feasable and effective and leads to extended overall survival compared to historical data. As more progress is being made, the variety of therapeutic options makes it challenging in clinical practice to choose the best treatment option for the individual mRCC patient. This review revisits results from the pivotal trials of currently approved therapeutic agents (in chronological order of their approval) in context with latest results from current clinical trials.
Cite this paper
H. Kirchner, A. Heidenreich and B. Brehmer, "Treatment Efficacy of Targeted Therapies for Metastatic Renal Cell Carcinoma—A Review after Seven Years of Experience," Journal of Cancer Therapy, Vol. 4 No. 9, 2013, pp. 22-29. doi: 10.4236/jct.2013.49A2004.
H. Kirchner, A. Heidenreich and B. Brehmer, "Treatment Efficacy of Targeted Therapies for Metastatic Renal Cell Carcinoma—A Review after Seven Years of Experience," Journal of Cancer Therapy, Vol. 4 No. 9, 2013, pp. 22-29. doi: 10.4236/jct.2013.49A2004.
References
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Esteban, “Temsirolimus vs Sorafenib as Second Line Therapy in Metastatic Renal Cell Carcinoma: Results from the INTORSECT Trial,” Annals of Oncology, Vol. 23, 2012, Article ID: LBA22. [33] B. Escudier, C. Szczylik, T. E. Hutson, et al., “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, Vol. 27, No. 8, 2009, pp. 1280-1289. http://dx.doi.org/10.1200/JCO.2008.19.3342 [34] G. Procopio, E. Verzoni and F. de Braud, “Targeted Therapies and Survival: What We Can Learn from Studies in Advanced Renal Cell Carcinoma,” Oncology, Vol. 84, No. 1, 2013, pp. 39-42.
http://dx.doi.org/10.1159/000342768 [35] M. P. Sablin, S. Negrier, A. Ravaud, et al., “Sequential Sorafenib and Sunitinib for Renal Cell Carcinoma,” Journal of Urology, Vol. 182, 2009, pp. 29-34. http://dx.doi.org/10.1016/j.juro. 2009.02.119 [36] V. Grunwald, C. Seidel, M. Fenner, et al., “Treatment of Everolimus-Resistant Metastatic Renal Cell Carcinoma with VEGF-Targeted Therapies,” British Journal of Cancer, Vol. 105, 2011, pp. 1635-1639. http://dx.doi.org/10.1038/bjc.2011.389 [37] N. Calvani, F. Morelli, S. Leo, et al., “Sequential Use of Sorafenib and Sunitinib in Advanced Renal Cell Carcinoma: Does the Order of Sequencing Matter?” Medical Oncology, Vol. 29, No. 3, 2012, pp. 1908-1913. http://dx.doi.org/10.1007/s12032-011-0048-0 [38] F. Stenner, R. Chastonay, H. Liewen, et al., “A Pooled Analysis of Sequential Therapies with Sorafenib and Sunitinib in Metastatic Renal Cell Carcinoma,” Oncology, Vol. 82, 2012, pp. 333-340. http://dx.doi.org/10.1159/000338001 [39] A. Ambring, I. Bjorholt, E. Lesen, et al., “Treatment with Sorafenib and Sunitinib in Renal Cell Cancer: A Swedish Register-Based Study,” Medical Oncology, Vol. 30, 2013, p. 331. http://dx.doi.org/ 10.1007/s12032-012-0331-8 [40] C. Porta, G. Procopio, G. Carteni, et al., “Sequential Use of Sorafenib and Sunitinib in Advanced Renal-Cell Carcinoma (RCC): An Italian Multicentre Retrospective Analysis of 189 Patient Cases,” BJU Internatioanl, Vol. 108, No. 8b, 2011, pp. E250-E257. http://dx.doi.org/10.1111/j.1464-410X.2011.10186.x [41] B. Ljungberg, K. Bensalah and A. Bex, “Guidelines on Renal Cell Carcinoma,” European Association of Urology, 2013. [42] SWITCH-I: Sequential Study to Treat Renal Cell Carcinoma.
http://clinicaltrials.gov/ct2/show/NCT00732914?term=NCT00732914&rank=1
[1] N. J. Vogelzang and W. M. Stadler, “Kidney Cancer,” Lancet, Vol. 352, No. 9141, 1998, pp. 1691-1696. http://dx.doi.org/10.1016/S0140-6736(98)01041-1 [2] B. Ljungberg, “Prognostic Factors in Renal Cell Carcinoma,” Scandinavian Journal of Surgery, Vol. 93, 2004, pp. 118-125. [3] S. Waalkes, A. J. Schrader and M. A. Kuczyk, “Current Treatment Options for Disseminated Renal Cell Carcinoma,” European Urology Supplements, Vol. 11, No. 3, 2012, pp. 73-78. http://dx.doi.org/ 10.1016/j.eursup.2012.04.001 [4] Y. G. Najjar and B. I. Rini, “Novel Agents in Renal Carcinoma: A Reality Check,” Therapeutic Advances in Medical, Vol. 4, No. 4, 2012, pp. 183-194. http://dx.doi.org/10.1177/1758834012443725 [5] B. Escudier, T. Eisen, W. M. Stadler, et al., “Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma,” The New England Journal of Medicine, Vol. 356, 2007, pp. 125-134. http://dx.doi.org/10.1056/ NEJMoa060655 [6] B. Escudier, T. Eisen, W. M. Stadler, et al., “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, Vol. 27, No. 20, 2009, pp. 3312-3318. http://dx.doi.org/10.1200/ JCO.2008.19.5511 [7] W. M. Stadler, R. A. Figlin, D. F. McDermott, et al., “Safety and Efficacy Results of the Advanced Renal Cell Carcinoma Sorafenib Expanded Access Program in North America,” Cancer, Vol. 116, No. 5, 2010, pp. 1272-1280. http://dx.doi.org/10.1002/cncr.24864 [8] J. Beck, G. Procopio, E. Bajetta, et al., “Final Results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) Expanded-Access Study: A Large Open-Label Study in Diverse Community Settings,” Annals of Oncology, Vol. 22, No. 8, 2011, pp. 1812-1823. http://dx.doi.org/10.1093/ annonc/mdq651 [9] R. J. Motzer, T. E. Hutson, P. Tomczak, et al., “Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma,” The New England Journal of Medicine, Vol. 356, 2007, pp. 115-124. http://dx.doi.org/ 10.1056/NEJMoa065044 [10] R. J. Motzer, T. E. Hutson, P. Tomczak, et al., “Overall Survival and Updated Results for Sunitinib Compared with Interferon Alfa in Patients with Metastatic Renal Cell Carcinoma,” Journal of Clinical Oncology, Vol. 27, No. 22, 2009, pp. 3584-3590. http://dx.doi.org/10.1200/JCO.2008.20.1293 [11] L. Gore, R. Bukowski and C. Porta, “Sunitinib Global Expanded-Access Trial in Metastatic Renal Cell Carcinoma (Mrcc)—Final Results,” Annals of Oncology, Vol. 23, 2012, p. 820. [12] B. Escudier, A. Pluzanska, P. Koralewski, et al., “Bevacizumab plus Interferon Alfa-2a for Treatment of Metastatic Renal Cell Carcinoma: A Randomised, Double-Blind Phase III Trial,” Lancet, Vol. 370, No. 9605, 2007, pp. 2103-2111. http://dx.doi.org/10.1016/S0140-6736(07)61904-7 [13] B. Escudier, J. Bellmunt, S. Negrier, et al., “Phase III Trial of Bevacizumab plus Interferon Alfa-2a in Patients with Metastatic Renal Cell Carcinoma (AVOREN): Final Analysis of Overall Survival,” Journal of Clinical Oncology, Vol. 28, No. 13, 2010, pp. 2144-2150. http://dx.doi.org/10.1200/JCO.2009.26.7849 [14] B. I. Rini, S. Halabi, J. E. Rosenberg, et al., “Bevacizumab plus Interferon Alfa Compared with Interferon Alfa Monotherapy in Patients with Metastatic Renal Cell Carcinoma: CALGB 90206,” Journal of Clinical Oncology, Vol. 26, No. 33, 2008, pp. 5422-5428. http://dx.doi.org/10.1200/JCO. 2008.16.9847 [15] B. I. Rini, S. Halabi, J. E. Rosenberg, et al., “Phase III Trial of Bevacizumab plus Interferon Alfa versus Interferon Alfa Monotherapy in Patients with Metastatic Renal Cell Carcinoma: Final Results of CALGB 90206,” Journal of Clinical Oncology, Vol. 28, No. 13, 2010, pp. 2137-2143. http://dx.doi.org/ 10.1200/JCO.2009.26.5561 [16] G. Hudes, M. Carducci, P. Tomczak, et al., “Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma,” The New England Journal of Medicine, Vol. 356, 2007, pp. 2271-2281. http://dx.doi.org/10.1056/NEJMoa066838 [17] R. J. Motzer, B. Escudier, S. Oudard, et al., “Efficacy of Everolimus in Advanced Renal Cell Carcinoma: A Double-Blind, Randomised, Placebo-Controlled Phase III Trial,” Lancet, Vol. 372, No. 9637, 2008, pp. 449-456. http://dx.doi.org/10.1016/S0140-6736(08)61039-9 [18] R. J. Motzer, B. Escudier, S. Oudard, et al., “Phase 3 Trial of Everolimus for Metastatic Renal Cell Carcinoma: Final Results and Analysis of Prognostic Factors,” Cancer, Vol. 116, No. 18, 2010, pp. 4256-4265. http://dx.doi.org/10.1002/cncr.25219 [19] C. N. Sternberg, I. D. Davis, J. Mardiak, et al., “Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial,” Journal of Clinical Oncology, Vol. 28, No. 6, 2010, pp. 1061-1068. http://dx.doi.org/10.1200/JCO.2009.23.9764 [20] C. N. Sternberg, R. E. Hawkins, J. Wagstaff, et al., “A Randomised, Double-Blind Phase III Study of Pazopanib in Patients with Advanced and/or Metastatic Renal Cell Carcinoma: Final Overall Survival Results and Safety Update,” European Journal of Cancer, Vol. 49, No. 6, 2013, pp. 1287-1296. http://dx.doi.org/10.1016/j.ejca.2012.12.010 [21] R. Motzer, T. E. Hutson and J. Reeves, “Randomized, Open Label, Phase III Trial of Pazopanib versus Sunitinib in First-Line Treatment of Patients with Metastatic Renal Cell Carcinoma (mRCC): Results of the COMPARZ Trial,” Annals of Oncology, Vol. 23, 2012, Article ID: LBA8. [22] B. I. Rini, B. Escudier, P. Tomczak, et al., “Comparative Effectiveness of Axitinib versus Sorafenib in Advanced Renal Cell Carcinoma (AXIS): A Randomised Phase 3 Trial,” Lancet, Vol. 378, No. 9807, 2011, pp. 1931-1939. http://dx.doi.org/10.1016/S0140-6736(11)61613-9 [23] R. Motzer, B. Escudier and P. Tomczak, “Axitinib vs Sorafenib for Advanced Renal Cell Carcinoma: Phase III Overall Survival Results and Analysis of Prognostic Factors,” Annals of Oncology, Vol. 23, 2012. [24] R. J. Motzer, B. Escudier, P. Tomczak, et al., “Axitinib versus Sorafenib as Second-Line Treatment for Advanced Renal Cell Carcinoma: Overall Survival Analysis and Updated Results from a Randomised Phase 3 Trial,” Lancet Oncology, Vol. 14, No. 6, 2013, pp. 552-562. http://dx.doi.org/10.1016/S1470-2045(13)70093-7 [25] R. J. Motzer, T. E. Hutson, M. R. Olsen, et al., “Randomized Phase II Trial of Sunitinib on an Intermittent versus Continuous Dosing Schedule as First-Line Therapy for Advanced Renal Cell Carcinoma,” Journal of Clinical Oncology, Vol. 30, No. 12, 2012, pp. 1371-1377. http://dx.doi.org/ 10.1200/JCO.2011.36.4133 [26] B. Rini, C. Szczylik, N. M. Tannir, et al., “AMG 386 in Combination with Sorafenib in Patients with Metastatic Clear Cell Carcinoma of the Kidney: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study,” Cancer, Vol. 118, No. 24, 2012, pp. 6152-6161. http://dx.doi.org/ 10.1002/cncr.27632 [27] R. Motzer, D. Nosov and T. Eisen, “Tivozanib versus Sorafenib as Initial Targeted Therapy for Patients with Advanced Renal Cell Carcinoma: Results from a Phase III Randomized, Open-Label, Multicenter Trial,” Journal of Clinical Oncology, Vol. 30, 2012. [28] T. E. Hutson, D. Nosov and T. Eisen, “Subgroup Analyses of a Phase III Trial Comparing Tivozanib Hydrochloride versus Sorafenib as Initial Targeted Therapy for Patients (pts) with Metastatic Renal Cell Carcinoma (mRCC),” Journal of Clinical Oncology, Vol. 31, 2013. [29] R. Motzer, T. Eisen and T. E. Hutson, “Overall Survival Results from a Phase III Study of Tivozanib Hydrochloride versus Sorafenib in Patients with Renal Cell Carcinoma,” Journal of Clinical Oncology, Vol. 31, 2013. [30] T. E. Hutson, J. Gallardo and V. Lesovoy, “Axitinib versus Sorafenib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma (mRCC),” Journal of Clinical Oncology, Vol. 31, 2013. [31] B. Rini, J. Bellmunt and J. Clancy, “Randomized Phase IIIb Trial of Temsirolimus and Bevacizumab versus Interferon and Bevacizumab in Metastatic Renal Cell Carcinoma: Results from INTORACT,” ESMO, 2012, Article ID: LBA1487. [32] T. E. Hutson, B. Escudier and E. Esteban, “Temsirolimus vs Sorafenib as Second Line Therapy in Metastatic Renal Cell Carcinoma: Results from the INTORSECT Trial,” Annals of Oncology, Vol. 23, 2012, Article ID: LBA22. [33] B. Escudier, C. Szczylik, T. E. Hutson, et al., “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, Vol. 27, No. 8, 2009, pp. 1280-1289. http://dx.doi.org/10.1200/JCO.2008.19.3342 [34] G. Procopio, E. Verzoni and F. de Braud, “Targeted Therapies and Survival: What We Can Learn from Studies in Advanced Renal Cell Carcinoma,” Oncology, Vol. 84, No. 1, 2013, pp. 39-42.
http://dx.doi.org/10.1159/000342768 [35] M. P. Sablin, S. Negrier, A. Ravaud, et al., “Sequential Sorafenib and Sunitinib for Renal Cell Carcinoma,” Journal of Urology, Vol. 182, 2009, pp. 29-34. http://dx.doi.org/10.1016/j.juro. 2009.02.119 [36] V. Grunwald, C. Seidel, M. Fenner, et al., “Treatment of Everolimus-Resistant Metastatic Renal Cell Carcinoma with VEGF-Targeted Therapies,” British Journal of Cancer, Vol. 105, 2011, pp. 1635-1639. http://dx.doi.org/10.1038/bjc.2011.389 [37] N. Calvani, F. Morelli, S. Leo, et al., “Sequential Use of Sorafenib and Sunitinib in Advanced Renal Cell Carcinoma: Does the Order of Sequencing Matter?” Medical Oncology, Vol. 29, No. 3, 2012, pp. 1908-1913. http://dx.doi.org/10.1007/s12032-011-0048-0 [38] F. Stenner, R. Chastonay, H. Liewen, et al., “A Pooled Analysis of Sequential Therapies with Sorafenib and Sunitinib in Metastatic Renal Cell Carcinoma,” Oncology, Vol. 82, 2012, pp. 333-340. http://dx.doi.org/10.1159/000338001 [39] A. Ambring, I. Bjorholt, E. Lesen, et al., “Treatment with Sorafenib and Sunitinib in Renal Cell Cancer: A Swedish Register-Based Study,” Medical Oncology, Vol. 30, 2013, p. 331. http://dx.doi.org/ 10.1007/s12032-012-0331-8 [40] C. Porta, G. Procopio, G. Carteni, et al., “Sequential Use of Sorafenib and Sunitinib in Advanced Renal-Cell Carcinoma (RCC): An Italian Multicentre Retrospective Analysis of 189 Patient Cases,” BJU Internatioanl, Vol. 108, No. 8b, 2011, pp. E250-E257. http://dx.doi.org/10.1111/j.1464-410X.2011.10186.x [41] B. Ljungberg, K. Bensalah and A. Bex, “Guidelines on Renal Cell Carcinoma,” European Association of Urology, 2013. [42] SWITCH-I: Sequential Study to Treat Renal Cell Carcinoma.
http://clinicaltrials.gov/ct2/show/NCT00732914?term=NCT00732914&rank=1