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Renal cell carcinoma: An update for the practicing urologist |
Sumanta K. Pal1, Paulo Bergerot2, Robert A. Figlin3
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1. Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA;
2. Health Department of Federal District (SES)-HRAN, Brasilia, Brazil;
3. Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA |
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Abstract Systemic therapy for metastatic renal cell carcinoma (mRCC) has evolved drastically, with agents targeting vascular endothelial growth factor (VEGF) and the mammalian target of rapamycin (mTOR) now representing a standard of care. The present paper is to review the current status of relevant clinical trials that were either recently completed or ongoing. (1) Though observation remains a standard of care following resection of localized disease, multiple trials are underway to assess VEGF-and mTOR-directed therapies in this setting. (2) While the preponderance of retrospective data favors cytoreductive nephrectomy in the context of targeted agents, prospective data to support this approach is still forthcoming. (3) The first-line management of mRCC may change substantially with multiple studies exploring vaccines, immune checkpoint inhibitors, and novel targeted agents currently underway. In general, prospective studies that will report within the next several years will be critical in defining the role of adjuvant therapy and cytoreductive nephrectomy. Over the same span of time, the current treatment paradigm for first-line therapy may evolve.
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Received: 02 August 2014
Published: 06 February 2015
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Corresponding Authors:
Sumanta K. Pal
E-mail: spal@coh.org
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[1] |
Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol 2004;22:4991-5004.
|
[2] |
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.
|
[3] |
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: 3584-90.
|
[4] |
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;28:2144-50.
|
[5] |
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;378:1931-9.
|
[6] |
Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebocontrolled phase III trial. Lancet 2008;372:449-56.
|
[7] |
Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356: 2271-81.
|
[8] |
Pal SK, Haas NB. Adjuvant therapy for renal cell carcinoma: past, present, and future. Oncologist 2014;19:851-9.
|
[9] |
Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 2001;345:1655-9.
|
[10] |
Messing EM, Manola J, Wilding G, Propert K, Fleischmann J, Crawford ED, et al. Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial. J Clin Oncol 2003;21:1214-22.
|
[11] |
Pizzocaro G, Piva L, Colavita M, Ferri S, Artusi R, Boracchi P, et al. Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study. J Clin Oncol 2001;19:425-31.
|
[12] |
Clark JI, Atkins MB, Urba WJ, Creech S, Figlin RA, Dutcher JP, et al. Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: a cytokine working group randomized trial. J Clin Oncol 2003;21:3133-40.
|
[13] |
NCT00326898. Sunitinib malate or sorafenib tosylate in treating patients with kidney cancer that was removed by surgery. Available at: http://www.clinicaltrials.gov. [last accessed 09.12.13].
|
[14] |
Haas NB, Manola J, Ky B, Flaherty KT, Uzzo RG, Wood CG, et al. Cardiac safety analysis for a phase III trial of sunitinib (SU) or sorafenib (SO) or placebo (PLC) in patients (pts) with resected renal cell carcinoma (RCC). ASCO Meet Abstr 2012; 30:4500.
|
[15] |
Hall PS, Harshman LC, Srinivas S, Witteles RM. The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients. JACC Heart Fail 2013;1:72-8.
|
[16] |
NCT00492258. Sorafenib in treating patients at risk of relapse after undergoing surgery to remove kidney cancer. Available at: http://www.clinicaltrials.gov. [last accessed 09.12.13].
|
[17] |
Ritchie AWS, Meade AM, Choo L, Smith B, Welland A, Gregory A, et al. MRC SORCE trial: analysis of patients' presenting characteristics, tumor staging, and surgical approach. ASCO Meet Abstr 2014;32:496.
|
[18] |
NCT00375674. A clinical trial comparing efficacy and safety of sunitinib versus placebo for the treatment of patients at high risk of recurrent renal cell cancer. Available at: http://www.clinicaltrials.gov. [last accessed 09.12.13].
|
[19] |
NCT01120249. Everolimus in treating patients with kidney cancer who have undergone surgery. Available at: http://www.clinicaltrials.gov. [last accessed 09.12.13].
|
[20] |
Choueiri TK, Regan MM, Rosenberg JE, Oh WK, Clement J, Amato AM, et al. Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy. BJU Int 2010;106:772-8.
|
[21] |
Choueiri TK, Cheng S, Qu AQ, Pastorek J, Atkins MB, Signoretti S. Carbonic anhydrase IX as a potential biomarker of efficacy in metastatic clear-cell renal cell carcinoma patients receiving sorafenib or placebo: analysis from the treatment approaches in renal cancer global evaluation trial (TARGET). Urol Oncol 2013;31:1788-93.
|
[22] |
Belldegrun AS, Chamie K, Kloepfer P, Fall B, Bevan P, Storkel S, et al. ARISER: a randomized double blind phase III study to evaluate adjuvant cG250 treatment versus placebo in patients with high-risk ccRCC-results and implications for adjuvant clinical trials. ASCO Meet Abstr 2013;31:4507.
|
[23] |
Torrey R, Spiess PE, Pal SK, Josephson D. Role of surgery for locally advanced and metastatic renal cell carcinoma. J Natl Comp Canc Netw 2011;9:985-93.
|
[24] |
Kim D, Karam J, Wood C. Role of metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy. World J Urol 2014;32:631-42.
|
[25] |
Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol 2004;171:1071-6.
|
[26] |
Fujikawa K, Matsui Y, Miura K, Kobayashi T, Oka H, Fukuzawa S, et al. Serum immunosuppressive acidic protein and natural killer cell activity in patients with metastatic renal cell carcinoma before and after nephrectomy. J Urol 2000;164:673-5.
|
[27] |
Conti SL, Thomas IC, Hagedorn JC, Chung BI, Chertow GM, Wagner TH, et al. Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era. Int J Cancer 2014;134:2245-52.
|
[28] |
Abern MR, Scosyrev E, Tsivian M, Messing EM, Polascik TJ, Dudek AZ. Survival of patients undergoing cytoreductive surgery for metastatic renal cell carcinoma in the targetedtherapy era. Anticancer Res 2014;34:2405-11.
|
[29] |
Nelson RA, Vogelzang NJ, Pal SK. Impact of cytoreductive nephrectomy on disease-specific survival (DSS) in the cytokine and targeted therapy eras: age-and TNM-stage matched analysis of SEER data. ASCO Meet Abstr 2013;31: 4579.
|
[30] |
Heng DY, Wells JC, Rini BI, Beuselinck B, Lee JL, Knox JJ, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol 2014;66:704-10.
|
[31] |
NCT00930033. Randomized phase III trial evaluating the importance of nephrectomy in patients presenting with metastatic renal cell carcinoma treated with sunitinib. Available at: http://www.clinicaltrials.gov. [last accessed 14.08.14].
|
[32] |
NCT01099423. Randomized phase III trial comparing immediate versus deferred nephrectomy in patients with synchronous metastatic renal cell carcinoma. Available at: http://www.clinicaltrials.gov. [last accessed 08.08.14].
|
[33] |
National comprehensive cancer network clinical practice guidelines: renal cell carcinoma. Available at: http://www.nccn.org. [last accessed 29.03.14].
|
[34] |
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.
|
[35] |
Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002;20:289-96.
|
[36] |
Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med 2014;370:1769-70.
|
[37] |
Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med 2012;18:1254-61.
|
[38] |
NCT01265901. A randomized, controlled phase III study investigating IMA901 multipeptide cancer vaccine in patients receiving sunitinib as first-line therapy for advanced/metastatic renal cell carcinoma. Available at: http://clinicaltrials.gov/ct2/show/NCT01265901?termZIMA-901&rankZ2. [last accessed 22.10.12].
|
[39] |
Figlin RA, Amin A, Dudek A, Logan T, Lance RS, Holzbeierlein JM, et al. Phase II study combining personalized dendritic cell (DC)-based therapy, AGS-003, with sunitinib in metastatic renal cell carcinoma (mRCC). ASCO Meet Abstr 2012;30:348.
|
[40] |
Figlin RA, Nicolette CA, Amin A, Dudek A, Logan T, Lance RS, et al. Monitoring T-cell responses in a phase II study of AGS-003, an autologous dendritic cell-based therapy in patients with newly diagnosed advanced stage renal cell carcinoma in combination with sunitinib. ASCO Meet Abstr 2011;29:2532.
|
[41] |
NCT01582672. Phase 3 trial of autologous dendritic cell immunotherapy (AGS-003) plus standard treatment of advanced renal cell carcinoma (RCC) (ADAPT). Available at: http://www.clinicaltrials.gov. [last accessed 15.12.13].
|
[42] |
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;27:5794-9.
|
[43] |
Pal SK, Hu A, Chang M, Figlin RA. Programmed death-1 inhibition in renal cell carcinoma: clinical insights and future directions. Clin Adv Hematol Oncol 2014;12:90-9.
|
[44] |
NCT01668784. Study of nivolumab (BMS-936558) vs. everolimus in pre-treated advanced or metastatic clear-cell renal cell carcinoma (CheckMate 025). Available at: http://www.clinicaltrials.gov. [last accessed 20.02.14].
|
[45] |
Choueiri TK, Fishman MN, Escudier BJ, Kim JJ, Kluger HM, Stadler WM, et al. Immunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): biomarker-based results from a randomized clinical trial. ASCO Meet Abstr 2014:32.
|
[46] |
Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel T, Harrison MR, et al. Nivolumab for metastatic renal cell carcinoma (mRCC): results of a randomized, dose-ranging phase II trial. ASCO Meet Abstr 2014;32.
|
[47] |
Hammers HJ, Plimack ER, Infante JR, Ernstoff MS, Rini BI, McDermot DF, et al. Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). ASCO Meet Abstr 2014;32.
|
[48] |
Cho DC, Sosman JA, Sznol M, Gordon MS, Hollebecque A, Hamid O, et al. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with metastatic renal cell carcinoma (mRCC). ASCO Meet Abstr 2013;31:4505.
|
[49] |
A phase 2 study of MPDL3280A (an Engineered Anti-PDL1 Antibody) as monotherapy or in combination with avastin (bevacizumab) compared to sunitinib in patients with untreated advanced renal cell carcinoma. Available at: http://clinicaltrials.gov/ct2/show/NCT01984242. [last accessed 08.06.14].
|
[50] |
Choueiri TK, Pal SK, McDermott DF, Morrissey S, Ferguson KC, Holland J, et al. A phase I study of cabozantinib (XL184) in patients with renal cell cancer. Ann Oncol 2014;25: 1603-8.
|
[51] |
NCT01865747. A study of cabozantinib (XL184) vs everolimus in subjects with metastatic renal cell carcinoma (METEOR). Available at: http://www.clinicaltrials.gov. [last accessed on 20.02.14].
|
[52] |
NCT01835158. Randomized phase II study comparing cabozantinib (NSC #761968) with commercially supplied sunitinib in patients with previously untreated locally advanced or metastatic renal cell carcinoma. Available at: http://www.clinicaltrials.gov. [last accessed 14.08.14].
|
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