Renal Cell Carcinoma Treatment Regimens

SEE BELOW THE CHART TO SEE GENITOURINARY CANCER DRUG MONOGRAPHS.

Renal Cell Carcinoma Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Adjuvant Therapy for Patients With Clear Cell Histology and High-Risk Disease1

Note: All recommendations are Category 2A unless otherwise indicated. Regimens listed alphabetically by category and preference.

REGIMEN

DOSING

Sunitinib (Category 2B)2-6

Sunitunib 50 mg orally once daily with or without food for 4 weeks, followed by 2 weeks off for 1 year.

Relapse or Stage IV: First-line Therapy for Patients with Clear Cell Histology1

Pembrolizumab + Axitinib (Category 2A; preferred for favorable risk); (Category 1; preferred for poor/intermediate risk) 7,8

Day 1: Pembrolizumab 200mg IV

AND

Days 1–21: Axitinib 5mg orally twice daily.a

Repeat cycle every 3 weeks.

Pazopanib (Category 2A; preferred for favorable risk); (Category 1 for poor/intermediate risk)9-12

Pazopanib 800mg orally once daily without food.

Sunitinib (Category 2A; preferred for favorable risk); (Category 1 for poor/intermediate risk)2,13,14

Sunitinib 50mg orally once daily with or without food for 4 weeks, followed by 2 weeks off.

Bevacizumab + IFN alfa-2B (Category 1)15-17

Day 1: Bevacizumab 10mg/kg IV

AND

Days 1,3,5,8,10,12: Interferon alfa-2B 9 million units subcutaneous every 2 weeks.

Temsirolimus (Category 1 for poor/intermediate risk)18-20

Temsirolimus 25mg IV over 30–60 minutes once weekly.

Nivolumab/Ipilimumab Followed by Nivolumab (Category 1 [preferred] for poor/intermediate risk); Category 2A for favorable risk)21-23

Day 1: Nivolumab 3mg/kg IV over 30 minutes

AND

Day 1: Ipilimumab 1mg/kg IV over 30 minutes every 3 weeks for 4 cycles

FOLLOWED BY

Day 1: Nivolumab 240mg IV every 2 weeks

OR

Day 1: Nivolumab 480mg IV every 4 weeks.

High-dose Aldesleukin (IL-2) (for patients with excellent performance status and normal organ function)25,26

Days 1–5 and 15–19: IL-2 600,000 units/kg IV over 15 minutes every 8 hours (max 14 doses on days 1-5 and 14 doses on days 15-19 for a max 28 total doses per cycle).

Repeat cycle every 12 weeks for a max of 3 cycles.

Cabozantinib (Category 2A; preferred for poor/intermediate risk); (Category 2B for favorable risk)27-29

Cabozantinib 60mg orally once daily on an empty stomach.

Axitinib (Category 2B)30-32,b

Axitinib 5mg orally twice daily with or without food.

Relapse or Stage IV: Subsequent Therapy for Patients with Clear Cell Carcinoma1

Cabozantinib (Category 1; preferred)27-30

Cabozantinib 60mg orally once daily on an empty stomach.

Nivolumab (Category 1; preferred)22,33,34

Day 1: Nivolumab 240mg IV over 30 minutes every 2 weeks

OR

Day 1: Nivolumab 480mg IV over 30 minutes every 4 weeks.

Axitinib (Category 1)30-32,35,b

Axitinib 5mg orally twice daily with or without food.

Lenvatinib + Everolimus (Category 1)36-38

Lenvatinib 18mg orally once daily with or without food.

Nivolumab/Ipilimumab (Category 2A; preferred)21-24

Day 1: Nivolumab 3mg/kg IV over 30 minutes

AND

Day 1: Ipilimumab 1mg/kg IV over 30 minutes every 3 weeks for 4 cycles

FOLLOWED BY

Day 1: Nivolumab 240mg IV every 2 weeks

OR

Day 1: Nivolumab 480mg IV every 4 weeks.

Pembrolizumab + Axitinib7,8

Day 1: Pembrolizumab 200mg IV

AND

Days 1-21: Axitinib 5mg orally twice daily.a

Repeat cycle every 3 weeks.

Everolimus37,39,40

Everolimus 10mg orally once daily with or without food.

Pazopanib9-12

Pazopanib 800mg orally once daily without food.

Sunitinib2,41,42

Sunitinib 50mg orally once daily with or without food for 4 weeks, followed by 2 weeks off.

Bevacizumab (Category 2B)15,43

Bevacizumab 10mg/kg IV every 2 weeks.

Sorafenib (Category 2B)44-48

Sorafenib 400mg orally twice daily without food.

High-dose Aldesleukin (IL-2) (for patients with excellent performance status and normal organ function) (Category 2B)23,24

Days 1-5 and 15-19: IL-2 600,000 units/kg IV over 15 minutes every 8 hours (max 14 doses on days 1-5 and 14 doses on days 15-19 for a max 28 total doses per cycle).

Repeat cycle every 12 weeks for a max of 3 cycles.

Temsirolimus (Category 2B)18,49,50

Temsirolimus 25mg IV over 30-60 minutes weekly.

Doxorubicin/Gemcitabine (for patients with disease characterized by predominant sarcomatoid features)(Category 2B)51,52

Day 1: Doxorubicin 50mg/m2 IV push

FOLLOWED BY

Day 1: Gemcitabine 1500-2000mg/m2 IV over 60 minutes every 2 or 3 weeks.

Gemcitabine/Sunitinib (for patients with disease characterized by predominant sarcomatoid features) (Category 2B)53

Days 1 and 8: Gemcitabine 1000mg/m2 IV over 30 minutes

AND

Days 1-14: Sunitinib 37.5mg orally once daily with or without food every 3 weeks.

Relapse or Stage IV: Systemic Therapy for Patients with Non-Clear Cell Histology1

Sunitinib (preferred)2,42,54

Sunitinib 50mg orally once daily with or without food for 4 weeks, followed by 2 weeks off.

Temsirolimus (Category 1: poor-prognosis patients; Category 2A: selected patients of other risk groups)18-20,49,50

Temsirolimus 25mg IV over 30–60 minutes weekly.

Cabozantinib27,28

Cabozantinib 60mg orally once daily on an empty stomach.

Everolimus37,39,40

Everolimus 10mg orally once daily with or without food.

Axitinib30,31,b

Axitinib 5mg orally twice daily with or without food.

Bevacizumab15,43,54

Bevacizumab 15mg/kg IV every 3 weeks.

Erlotinib56,57

Erlotinib 150mg orally once daily on an empty stomach.

Lenvatinib + Everolimus36-38

Lenvatinib 18mg orally once daily with or without food

AND

Everolimus 5mg orally once daily with or without food.

Nivolumab22,33,34

Day 1: Nivolumab 240mg IV over 30 minutes every 2 weeks

OR

Day 1: Nivolumab 480mg IV over 30 minutes over 4 weeks.

Pazopanib9-12,58

Pazopanib 800mg orally once daily without food.

Bevacizumab + Erlotinib (for selected patients with advanced papillary RCC including HLRCC15,59,60,c

Days 1 and 15: Bevacizumab 10mg/kg IV

AND

Days 1-28: Erlotinib 150mg orally once daily on empty stomach.

Repeat cycle every 28 days.

Bevacizumab + Everolimus15,37,61

Days 1 and 15: Bevacizumab 10mg/kg IV

AND

Days 1-28: Everolimus 10mg orally once daily with or without food.

Repeat cycle every 28 days.

Doxorubicin/Gemcitabine (for patients with disease characterized by predominant sarcomatoid features) (Category 2B)51,52,d

Day 1: Doxorubicin 50mg/m2 IV push

FOLLOWED BY

Day 1: Gemcitabine 1500-2000mg/m2 over 60 minutes every 2 or 3 weeks.

Gemcitabine/Sunitinib (for patients with disease characterized by predominant sarcomatoid features) (Category 2B)53

Days 1 and 8: Gemcitabine 1000mg/m2 IV over 30 minutes

AND

Days 1-14: Sunitinib 37.5mg orally once daily with or without food every 3 weeks.

Gemcitabine/Carboplatin (for patients with collecting duct or medullary subtypes only; Category 2A)62

Days 1 and 8: Gemcitabine 1250mg/m2 IV over 30 minutes

AND

Day 1: Carboplatin AUC5 IV over 30 minutes every 3 weeks for 6 cycles.

Paclitaxel/Carboplatin (for patients with collecting duct or medullary subtypes only; Category 2A)63

Day 1: Paclitaxel 175mg/m2 IV over 3 hours

FOLLOWED BY

Day 1: Carboplatin AUC5-6 IV over 30 minutes every 3 weeks for 6 cycles.

Gemcitabine/Cisplatin (for patients with collecting duct or medullary subtypes only; Category 2A)62

Days 1 and 8: Gemcitabine 1250mg/m2 over 30 minutes

AND

Day 1: Cisplatin 70mg/m2 IV over 60 minutes every 3 weeks for 6 cycles.

 a The dose of axitinib can be increased to 7mg, then 10mg, twice daily if safety criteria are met and reduced to 3mg, then 2mg, twice daily to manage toxic effects.

 b The dose of axitinib is typically started at 5mg twice daily and then titrated to a maximum of 10mg twice daily based on response or toxicity.

 c HLRCC: Hereditary leiomyomatosis and renal cell cancer.

 d Continue until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose.

References

  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Kidney. v 4.2019. Available at: http://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed April 25, 2019.

  2. Sutent (sunitinib) [package insert]. New York, NY: Pfizer Labs; 2017.

  3. Haas NB, Manola J, Uzzo RG, et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, ­placebo-controlled, randomised, phase 3 trial. Lancet. 2016;387:2008-2016.

  4. Ravaud A, Motzer RJ, Pandha HS, et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. 2016;375:2246-2254.

  5. Motzer RJ, Ravaud A, Patard JJ, et al. Adjuvant sunitinib for high-risk renal cell ­carcinoma after nephrectomy: Subgroup analyses and updated overall survival ­results. Eur Urol. 2018;73:62-68.

  6. Haas NB, Manola J, Dutcher JP, et al. Adjuvant treatment for high-risk clear cell renal cancer: Updated results of a high-risk subset of the ASSURE randomized trial. JAMA Oncol. 2017;3:1249-1252.

  7. Pembrolizumab (Keytruda) [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2019.

  8. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116-1127.

  9. Votrient (pazopanib) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2016.

10. Sternberg CN, Davis ID, Mardiak J et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28:1061-1068.

11. Sternberg CN, Hawkins RE, Wagstaff J, 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. Eur J Cancer. 2013;49:1287-1296.

12. Motzer RJ, Hutson TE, McCann L, et al. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014;370:1769-1770.

13. Gore ME, Szczylik C, Porta C, et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009;10:757-763.

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

15. Avastin (bevacizumab) [package insert]. San Francisco, CA: Genentech; 2017.

16. Escudier B, Pluzanska A, Koralewski P, 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;370:2103-2111.

17. Rini BI, Halabi S, Rosenberg JE, 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(13):2137-2143.

18. Torisel (temsirolimus) [package insert]. Philadelphia, PA: Wyeth; 2018.

19. Hudes G, Carducci M, Tomczak P, et al; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271-2281.

20. Dutcher JP, de Souza P, McDermott D, et al. Effect of temsirolimus versus interferon-­alpha on outcome of patients with advanced renal cell carcinoma of different tumor histologies. Med Oncol. 2009;26:202-209.

21. Yervoy (ipilimumab) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.; 2018.

22. Opdivo (nivolumab) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.; 2018.

23. Hammers HJ, Plimack ER, Infante JR, et al. Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma: The CheckMate 016 study. J Clin Oncol. 2017;35:3851-3858.

24. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277-1290.

25. Proleukin [package insert]. San Diego, CA: Prometheus Laboratories; 2016.

26. McDermott DF, Regan MM, Clark JI, et al. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol. 2005;23:133-141.

27. Cabometryx (carbozantinib) [package insert]. Alameda, CA: Exelixis, Inc.: 2019.

28. Choueiri TK, Escudier B, Powles T, et al; METEOR Investigators. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1814-1823.

29. Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus sunitinib as initial ­targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the Alliance A031203 CABOSUN trial. J Clin Oncol. 2017;35:591-597.

30. Inlyta (axitinib) [package insert]. New York, NY: Pfizer Inc; 2018.

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

32. Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013;14:1287-1294.

33. Motzer RJ, Escudier B, McDermott DF, et al; CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803-1813.

34. Zhao X, Ivaturi V, Gopalakrishnan M, et al. A model-based exposure-response (E-R) assessment of a nivolumab (NIVO) 4-weekly (Q4W) dosing schedule across multiple tumor types. Cancer Res. 2017;77(13_suppl):CT101.

35. Motzer RJ, Escudier B, Tomczak P, 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 Oncol. 2013;14:552-562

36. Lenvima (lenvatinib) [package insert]. Woodcliff Lake, NJ: Eisai Inc.; 2018

37. Afinitor (everolimus) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2018

38. Motzer RJ, Hutson TE, Glen H, 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(:1473-1482.

39. Motzer RJ, Escudier B, Oudard 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;372:449-456.

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

41. Motzer RJ, Rini BI, Bukowski RM, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 2006;295:2516-2524.

42. Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24:16-24.

43. Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349:427-434.

44. Nexavar (sorafenib) [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2018

45. Escudier B, Eisen T, Sta dler WM, et al. Sorafenib in advanced clear cell renal-cell carcinoma. N Engl J Med. 2007;356:125-134.

46. Di Lorenzo G, Carteni G, Autorino R, et al. Phase II study of sorafenib in patients with sunitinib-refractory metastatic renal cell cancer. J Clin Oncol. 2009;27:4469-4474.

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

48. Escudier B, Szczylik C, Hutson TE, 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;27:1280-1289.

49. Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol. 2004;22:909-918.

50. Hutson TE, Escudier B, Esteban E, et al. Temsirolimus vs Sorafenib as Second Line Therapy in Metastatic Renal Cell Carcinoma: Results from the INTORSECT Trial [abstract]. Ann Oncol. 2012;23:Abstract: LBA22.

51. Dutcher JP, Nanus D. Long-term survival of patients with sarcomatoid renal cell cancer treated with chemotherapy. Med Oncol. 2011;28:1530-1533.

52. Nanus DM, Garino A, Milowsky MI, et al. Active chemotherapy for sarcomatoid and rapidly progressing renal cell carcinoma. Cancer. 2004;101:1545-1551.

53. Michaelson MD, McKay RR, Werner L, et al. Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Cancer. 2015;121:3435-3443.

54. Lee JL, Ahn JH, Lim HY, et al. Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma. Ann Oncol. 2012;23:2108-2114.

55. Irshad T, Olencki T, Zynger DL, et al. Bevacizumab in metastatic papillary cell carcinoma (PRCC) [abstract]. J Clin Oncol. 2011;29(15_suppl):Abstract: e15158.

56. Erlotinib (Tarceva) [package insert]. South San Francisco, CA: Genentech, Inc. 2016.

57. Gordon MS, Hussey M, Nagle RB, et al. Phase II study of erlotinib in patients with wlocally advanced or metastatic papillary histology renal cell cancer: SWOG S0317. J Clin Oncol. 2009;27:5788-5793.

58. Buti S, Bersanelli M, Maines F, et al. First-line pazopanib in non-clear cell renal carcinoma: The Italian retrospective multicenter PANORAMA study. J Clin Oncol. 2016;34(suppl):abstr e16081.

59. Singer EA, Friend JC, Hawks G, et al. A phase II study of bevacizumab and erlotinib in subjects with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC) or sporadic papillary renal cell cancer (RCC). J Clin Oncol. 2012;30(15_suppl):abstr TPS4680.

60. Srinivasan R, Su D, Stamatakis L, et al. Mechanism based targeted therapy for hereditary leiomyomatosis and renal cell cancer (HLRCC) and sporadic papillary renal cell carcinoma: interim |results from a phase 2 study of bevacizumab and erlotinib [abstract]. Eur J Cancer. 2014;50:8.

61. Voss MH, Molina AM, Chen YB, et al. Phase II trial and correlative genomic analysis of everolimus plus bevacizumab in advanced non-clear cell renal cell carcinoma. J Clin Oncol. 2016;34:3846-3853.

62. Oudard S, Banu E, Vieillefond A, et al. Prospective multicenter phase II study of gemcitabine plus platinum salt for metastatic collecting duct carcinoma: results of a GETUG (Groupe d’Etudes des Tumeurs Uro-Génitales) study. J Urol. 2007;177:1698-1702.

63. Gangireddy Vg, Liles GB, Sostre GD, Coleman T, et al. Response of metastatic renal medullary carcinoma to carboplatinum and paclitaxel chemotherapy. Clin Genitourin Cancer. 2012;10:134-1349.

(Revised 4/2019) © 2019 by Haymarket Media, Inc.

Genitourinary Cancer Drug Monographs

Bladder, Kidney, And Other Urologic Cancers

AFINITOR AVASTIN CABOMETYX
Cisplatin COSMEGEN DEPO-PROVERA
Doxorubicin HCl Doxorubicin HCl Solution INLYTA
LENVIMA NEXAVAR OPDIVO
PROLEUKIN SUTENT TECENTRIQ
Thiotepa TICE BCG TORISEL
VALSTAR VINCASAR PFS VOTRIENT

Prostate And Other Male Cancers

Bleomycin CASODEX Cisplatin
COSMEGEN DELESTROGEN ELIGARD
EMCYT ESTRACE ETOPOPHOS
FIRMAGON Flutamide IFEX
JEVTANA Leuprolide acetate LUPRON DEPOT 7.5mg
LUPRON DEPOT-3 MONTH 22.5mg LUPRON DEPOT-4 MONTH 30mg LUPRON DEPOT-6 MONTH 45mg
MENEST Mitoxantrone HCl NILANDRON
PREMARIN PROVENGE TAXOTERE
TOPOSAR TRELSTAR VANTAS
Vinblastine for injection Vinblastine injection XOFIGO
XTANDI ZOLADEX ZOLADEX 3-MONTH 10.8mg
ZYTIGA
Data provided by eMPR.com

This article originally appeared on Cancer Therapy Advisor