Sequential Therapy in Metastatic Renal Cell Carcinoma

Main Article Content

Bradford R. Hirsch
John M. Burke
Manish Agrawal
Ralph J. Hauke
Thomas E. Hutson
Gury Doshi
Mark T. Fleming
Nicholas J. Vogelzang

Keywords

kidney cancer, renal cell carcinoma, sequential therapy

Abstract

The treatment of metastatic renal cell carcinoma (mRCC) has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network's Genitourinary Research Committee. We outline our thought process in approaching sequential therapy of mRCC and the use of real-world data to inform our approach. We also highlight the evolving literature that will impact practicing oncologists in the near future.

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References

1. Centerwatch. Approved drugs by therapeutic area [Internet]. 2015 [cited 2015 June 22]. Available from: http://www.centerwatch.com/drug-information/fda-approvals/drug-areas.aspx?AreaID=12
2. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13. http://dx.doi.org/10.1056/NEJMoa1510665.
3. Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, et al; METEOR Investigators. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1814–23. http://dx.doi.org/10.1056/NEJMoa1510016.
4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Kidney Cancer. Washington, PA: NCCN; 2014.
5. European Association of Urology. Guidelins in Renal Cell Carcinoma. Arnheim, Netherlands: EAU; 2015.
6. Escudier B, Porta C, Schmidinger M, Algaba F, Patard JJ, Khoo V, et al; ESMO Guidelines Working Group. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii49–56. http://dx.doi.org/10.1093/annonc/mdu259.
7. Hirsch BR, Harrison MR, George DJ, Walker MS, Chen C, Korytowsky B, et al. Use of “Real-World” data to describe adverse events during the treatment of metastatic renal cell carcinoma in routine clinical practice. Med Oncol. 2014;31:156. http://dx.doi.org/10.1007/s12032-014-0156-8.
8. Iacovelli R, Cartenì G, Sternberg CN, Milella M, Santoni M, Di Lorenzo G, et al. Clinical outcomes in patients receiving three lines of targeted therapy for metastatic renal cell carcinoma: results from a large patient cohort. Eur J Cancer. 2013;49(9):2134–42. http://dx.doi.org/10.1016/j.ejca.2013.02.032.
9. Levy A, Menard J, Albiges L, Loriot Y, Di Palma M, Fizazi K, et al. Second line treatment of metastatic renal cell carcinoma: The Institut Gustave Roussy experience with targeted therapies in 251 consecutive patients. Eur J Cancer. 2013;49(8):1898–1904. http://dx.doi.org/10.1016/j.ejca.2013.02.003.
10. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. 1999;17:2530–40.
11. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. 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. J Clin Oncol. 2009;27(34):5794–99. http://dx.doi.org/10.1200/JCO.2008.21.4809.
12. Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US, et al. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer. 2008;113(2):293–301. http://dx.doi.org/10.1002/cncr.23552.
13. e-Patient Dave: A voice of patient engagement [Internet]. 2015 [cited 2015 June 22]. Available from: http://www.epatientdave.com/.
14. Motzer RJ, McCann L, Deen K. Pazopanib versus sunitinib in renal cancer. N Engl J Med. 2013;369(20):1970. http://dx.doi.org/10.1056/NEJMc1311795.
15. Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, et al. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014;32(14):1412–8. http://dx.doi.org/10.1200/JCO.2013.50.8267
16. Kalra S, Rini BI, Jonasch E. Alternate sunitinib schedules in patients with metastatic renal cell carcinoma. Ann Oncol. 2015;26(7):1300–4. http://dx.doi.org/10.1093/annonc/mdv030.
17. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271–81. http://dx.doi.org/10.1056/NEJMoa066838.
18. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(22): 3584–90. http://dx.doi.org/10.1200/JCO.2008.20.1293.
19. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28:1061–8. http://dx.doi.org/10.1200/JCO.2009.23.9764.
20. Clinicaltrials.gov. Pazopanib versus temsirolimus in poor-risk clear cell renal cell carcinoma [Internet]. 2015 [cited 2015 November 22]. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01392183.
21. Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol. 2010;28(13):2144–50. http://dx.doi.org/10.1200/JCO.2009.26.7849.
22. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, et al; AVOREN Trial Investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370(9605):2103–11. http://dx.doi.org/10.1016/S0140-6736(07)61904-7.
23. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008;26:5422–8. http://dx.doi.org/10.1200/JCO.2008.16.9847.
24. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Archer L, 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. J Clin Oncol. 2010;28:2137–43. http://dx.doi.org/10.1200/JCO.2009.26.5561.
25. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34. http://dx.doi.org/10.1056/NEJMoa060655.
26. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, 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. J Clin Oncol. 2009;27(20):3312–8. http://dx.doi.org/10.1200/JCO.2008.19.5511.
27. Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27:1280–9. http://dx.doi.org/10.1200/JCO.2008.19.3342.
28. McDermott DF, Manola J, Pins M, et al. The BEST trial (E2804): a randomized phase II study of VEGF, RAF kinase, and mTOR combination targeted therapy (CTT) with bevacizumab (bev), sorafenib (sor), and temsirolimus (tem) in advanced renal cell carcinoma (RCC). J Clin Oncol [ASCO abstract 345]. 2013;31(suppl 6).
29. Mitchell AP, Harrison MR, Walker MS, George DJ, Abernethy AP, Hirsch BR. Clinical trial participants with metastatic renal cell carcinoma differ from patients treated in real-world practice. J Oncol Pract. 2015;11:491–7. http://dx.doi.org/10.1200/JOP.2015.004929.
30. Hirsch BR, Jiao X, Wilson T, Hackshaw MD, Jonasch E, Ghate S, et al. Compartive effectiveness of pazopaninb and sunitinib as first line therapy for patients with advanced/metastatic renal cell carcinoma in a US community oncology setting. J Clin Oncol 34, 2016(suppl 2S; abstr 567).
31. Rothermundt C, Bailey A, Cerbone L, Eisen T, Escudier B, Gillessen S, et al. Algorithms in the first-line treatment of metastatic clear cell renal cell carcinoma–analysis using diagnostic nodes. Oncologist. 2015;20(9):1028–35. http://dx.doi.org/10.1634/theoncologist.2015-0145.
32. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931–9. http://dx.doi.org/10.1016/S0140-6736(11)61613-9.
33. Calvo E, Escudier B, Motzer RJ, Oudard S, Hutson TE, Porta C, et al. 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. 2012;48(3):333–9. http://dx.doi.org/10.1016/j.ejca.2011.11.027.
34. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372(9637):449–56. http://dx.doi.org/10.1016/S0140-6736(08)61039-9.
35. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al; RECORD‐1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer. 2010;116(18):4256–65. http://dx.doi.org/10.1002/cncr.25219.
36. Pal SK, Jonasch E, Signorovitch JE, Reichmann WM, Li N, Liu Z, et al. Real-world dosing and drug costs with everolimus or axitinib as second targeted therapy for advanced renal cell carcinoma: A retrospective chart review in the U.S. J Med Econ. 2016;11:1–7.
37. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10(12):2298–308. http://dx.doi.org/10.1158/1535-7163.MCT-11-0264.
38. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015;16:1473–82. http://dx.doi.org/10.1016/S1470-2045(15)00290-9.
39. Clinicaltrials.gov. Cabozantinib-s-malate or sunitinib malate in treating patients with previously untreated locally advanced or metastatic kidney cancer [Internet]. 2015 [cited 2015 November 22]. Available from: https://clinicaltrials.gov/show/NCT01835158.
40. Clinicaltrials.gov. Nivolumab in combination with sunitinib, pazopanib, or ipilimumab in subjects with metasatic rencal cell carcinoma (RCC)(CheckMate 016) [Internet]. 2015 [cited 2015 November 22]. Available from: https://clinicaltrials.gov/ct2/show/NCT01472081.
41. Amin A, Pilmack ER, Infante JR, et al. Nivolumab in combination with sunitinib or pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol 2014;32:5s.
42. Clinicaltrials.gov. Nivolumab combined with ipilumumab versus sunitinib in previoulsy untreated advanced or metastatic renal cell carcinoma (CheckMate 214) [Internet]. 2015 [cited 2015 November 22]. Available from: https://clinicaltrials.gov/ct2/show/NCT02231749/.
43. Clinicaltrials.gov. Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma [Internet]. 2015 [cited 2015 November 22]. Available from: https://clinicaltrials.gov/ct2/show/NCT01582672.
44. Rini B, Stenzi A, Zdroiowy R, Kogan M, Shkolnik S, Oudard S, et al. Results from an open-label, randomized, controlled Phase 3 study investigating IMA901 multipeptide cancer vaccine in patients receiving sunitinib as first line therapy for advanced/metastatic RCC. Presented at the European Cancer Congress, Viena, Austria, September 25–29, 2015.
45. Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369:722–31. http://dx.doi.org/10.1056/NEJMoa1303989.