Renal Cell Carcinoma Treatment Regimens

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.

Note: All recommendations are category 2A unless otherwise indicated.

▶Adjuvant Therapy for Patients With Clear Cell Histology1

REGIMEN

DOSING

Stage III Disease

Sunitinib (Category 3)2-5

Days 1-28: Sunitinib 50mg orally once daily.

Repeat 6-week cycle (4 weeks on followed by 2 weeks off treatment) for 1 year.

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

Favorable Risk

Preferred Regimens

Axitinib + Pembrolizumab6-10,a

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle very 3 weeks for a maximum of 35 cycles, with:

Days 1-28: Axitinib 5-10 mg twice daily.

Repeat cycle every 4 weeks.

Pazopanib9-12

Days 1-28: Pazopanib 800mg orally once daily.

Repeat cycle every 4 weeks.

Sunitinib2-4

Days 1-28: Sunitinib 50mg orally once daily.

Repeat cycle every 6 weeks (4 weeks on followed by 2 weeks off treatment).

Other Recommended Regimens

Axitinib + Avelumab6,13,14,a

Days 1 and 15: Avelumab 800mg IV over 60 minutes

Days 1-28: Axitinib 5-10mg orally twice daily.

Repeat cycle every 4 weeks.

Carbozantinib (Category 2B)15-17

Days 1-28: Cabozantinib 60mg orally once daily.

Repeat cycle every 4 weeks.

Ipilimumab + Nivolumab Followed By Nivolumab18-21

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

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

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

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Useful Under Certain Circumstances

Axitinib (Category 2B)6,22-24,a

Days 1-28: Axitinib 5-10mg orally twice daily.

Repeat cycle every 4 weeks.

High-dose Aldesleukin (IL-2)25,26,b

Days 1-5, 15-19: Aldesleukin (IL-2) 600,000units/kg IV over 15 minutes every 8 hours for a maximum of 28 doses per cycle.

Repeat 12-week cycle for a maximum of 3 cycles.

Poor/Intermediate Risk

Preferred Regimens

Axitinib + Pembrolizumab (Category 1)6-10,a

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for a maximum of 35 cycles, with:

Days 1-28: Axitinib 5-10mg orally once daily.

Repeat cycle every 4 weeks.

Cabozantinib15-17

Days 1-28: Cabozantinib 60mg orally once daily.

Repeat cycle every 4 weeks.

Ipilimumab + Nivolumab Followed By Nivolumab (Category 1)18-21

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

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1:Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

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

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Axitinib + Avelumab6,13,14,a

Days 1 and 15: Avelumab 800mg IV over 60 minutes

Days 1-28: Axitinib 5-10mg orally twice daily.

Repeat cycle every 4 weeks.

Pazopanib9-12

Days 1-28: Pazopanib 800mg orally once daily.

Repeat cycle every 4 weeks.

Sunitinib2-4

Days 1-28: Sunitinib 50mg orally once daily.

Repeat cycle every 6 weeks (4 weeks on followed by 2 weeks off treatment).

Useful Under Certain Circumstances

Axitinib (Category 2B)6,22-24,a

Days 1-28: Axitinib 5-10mg orally twice daily.

Repeat cycle every 4 weeks.

High-dose IL-225,26,b

Days 1-5, 15-19: Aldesleukin (IL-2) 600,000units/kg IV over 15 minutes every 8 hours for a maximum of 28 doses per cycle.

Repeat 12-week cycle for a maximum of 3 cycles.

Temsirolimus27-29

Day 1: Temsirolimus 25mg IV over 30-60 minutes.

Repeat cycle weekly.

▶Relapse or Stage IV: Subsequent Therapy for Clear Cell Histology1

Preferred Regimens

Cabozantinib (Category 1)15-17

Days 1-28: Cabozantinib 60mg orally once daily.

Repeat cycle every 4 weeks.

Ipilimumab + Nivolumab Followed By Nivolumab18-21

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

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

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

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Nivolumab (Category 1)19,30,31

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

Day 1:Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Axitinib (Category 1)6,22-24,a

Days 1-28: Axitinib 5-10mg orally twice daily.

Repeat cycle every 4 weeks.

Axitinib + Avelumab (Category 3)6,13,14,a

Days 1 and 15: Avelumab 800mg IV over 60 minutes

Days 1-28: Axitinib 5-10mg orally twice daily.

Repeat cycle every 4 weeks.

Axitinib + Pembrolizumab6-10,a

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for a maximum of 35 cycles, with:

Days 1-28: Axitinib 5-10mg orally once daily.

Repeat cycle every 4 weeks.

Everolimus32-34

Days 1-28: Everolimus 10mg orally once daily.

Repeat cycle every 4 weeks.

Lenvatinib + Everolimus (Category 1)32,35,36

Days 1-28: Everolimus 5mg orally once daily

Days 1-28: Lenvatinib 18mg orally once daily.

Repeat cycle every 4 weeks.

Pazopanib9-12

Days 1-28: Pazopanib 800mg orally once daily.

Repeat cycle every 4 weeks.

Sunitinib2-4

Days 1-28: Sunitinib 50mg orally once daily.

Repeat cycle every 6 weeks (4 weeks on followed by 2 weeks off treatment).

Useful Under Certain Circumstances

Bevacizumab or Biosimilar (Category 2B)40-42,c

Day 1: Bevacizumab 10mg/kg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

High-dose IL-2 (Category 2B)25,26,b

Days 1-5, 15-19: Aldesleukin (IL-2) 600,000units/kg IV over 15 minutes every 8 hours for a maximum of 28 doses per cycle.

Repeat 12-week cycle for a maximum of 3 cycles.

Sorafenib (Category 2B)37-39

Days 1-28: Sorafenib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Temsirolimus (Category 2B)27-29

Day 1: Temsirolimus 25mg IV over 30-60 minutes.

Repeat cycle weekly.

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

Preferred Regimens

Sunitinib2-4

Days 1-28: Sunitinib 50mg orally once daily.

Repeat cycle every 6 weeks (4 weeks on followed by 2 weeks off treatment).

Other Recommended Regimens

Cabozantinib15-17

Days 1-28: Cabozantinib 60mg orally once daily.

Repeat cycle every 4 weeks.

Everolimus32-34

Days 1-28: Everolimus 10mg orally once daily.

Repeat cycle every 4 weeks.

Useful Under Certain Circumstances

Axitinib6,22-24,a

Days 1-28: Axitinib 5-10mg orally twice daily.

Repeat cycle every 4 weeks.

Bevacizumab or Biosimilar40-42,c

Day 1: Bevacizumab 10mg/kg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Bevacizumab or Biosimilar + Erlotinib (for selected patients with advanced papillary RCC including HLRCC)40,43-45,,c,d

Days 1-28: Erlotinib 150mg orally once daily

Days 1 and 15: Bevacizumab 10mg/kg IV.

Repeat cycle every 4 weeks.

Bevacizumab or Biosimilar + Everolimus32,40,46,c

Days 1-28: Everolimus 10mg orally once daily

Days 1 and 15: Bevacizumab 10mg/kg IV.

Repeat cycle every 4 weeks.

Erlotinib43,47

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

Repeat cycle every 4 weeks.

Gemcitabine + Carboplatin (for patients with collecting duct or medullary subtypes only; Category 2A)48,e

Days 1 and 8: Gemcitabine 1,250mg/m2 IV over 30 minutes

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 3 weeks for 6 cycles.

Gemcitabine + Cisplatin (for patients with collecting duct or medullary subtypes only; Category 2A)48,e

Days 1 and 8: Gemcitabine 1,250mg/m2 over 30 minutes

Day 1: Cisplatin 70mg/m2 over 60 minutes.

Repeat cycle every 3 weeks for 6 cycles.

Lenvatinib + Everolimus32,35,36

Days 1-28: Everolimus 5mg orally once daily

Days 1-28: Lenvatinib 18mg orally once daily.

Repeat cycle every 4 weeks.

Nivolumab19,30,31

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Paclitaxel + Carboplatin (for patients with collecting duct or medullary subtypes only; Category 2A)49,e

Day 1: Paclitaxel 175mg/m2 IV over 3 hour, followed by:

Day 1: Carboplatin AUC 5-6 IV over 30 minutes.

Repeat cycle every 3 weeks for 6 cycles.

Pazopanib9-12

Days 1-28: Pazopanib 800mg orally once daily.

Repeat cycle every 4 weeks.

Temsirolimus (Category 1 for poor-prognosis risk group; Category 2A for other risk groups)27-29

Day 1: Temsirolimus 25mg IV over 30-60 minutes.

Repeat cycle weekly.

a  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.

b  For patients with excellent performance status and normal organ function.

c  Biosimilar options include: bevacizumab-awwb, bevacizumab-bvzr.

d  HLRCC: hereditary leiomyomatosis and renal cell cancer.

e  For collecting duct or medullary subtypes, partial responses have been observed with cytotoxic chemotherapy (carboplatin + gemcitabine, carboplatin + paclitaxel, or cisplatin + gemcitabine) and other platinum-based chemotherapies currently used for urothelial carcinomas. Oral targeted therapies generally do not produce responses in patients with renal medullary carcinoma. Outside of clinical trials, platinum-based chemotherapy regimens should be the preferred therapy for renal medullary carcinoma.

References

  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™ Kidney v2.2020. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed August 30, 2019.

  2. Sunitinib (Sutent) [package insert]. New York, NY: Pfizer Inc.; 2019.

  3. Motzer RJ, Hutson TE, Tomczak P, et al. v 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.

  4. 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.

  5. 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.

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

  7. Pembrolizumab (Keytruda) [package insert]. Whitehouse Station, NJ: Merck & Co.; 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. Pazopanib (Votrient) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2017.

10. 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.

11. 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.

12. 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_e16081).

13. Avelumab (Bavencio) [package insert]. Rockland, MA: EMD Serono, Inc.; 2019.

14. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1103-1115.

15. Carbozantinib (Cabometryx) [package insert]. Alameda, CA: Exelixis, Inc; 2019.

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

17. Martínez Chanzá N, Xie W, Asim Bilen M, et al. Cabozantinib in advanced non-clear-cell renal cell carcinoma: a multicentre, retrospective, cohort study. Lancet Oncol. 2019;20:581-590.

18. Ipilimumab (Yervoy) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.; 2019.

19. Nivolumab (Opdivo) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.; 2019.

20. 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.

21. 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.

22. 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.

23. 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.

24. Rini BI, Melichar B, Ueda T, et al. Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind phase 2 trial. Lancet Oncol. 2013;14:1233-1242.

25. Aldesleukin (Proleukin) [package insert]. Emeryville, CA Bayer Healthcare Pharmaceuticals Inc.; 2012.

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

27. Temsirolimus (Torisel) [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2018.

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

29. 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.

30. Long GV, Tykodi SS, Schneider JG, et al. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018;29:2208-2213.

31. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803-1813.

32. Everolimus (Affinitor) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2018.

33. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372:449-456.

34. 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.

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

36. 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.

37. Sorafnib (Nexavar) [package inset]. Whippany, NJ; Bayer Healthcare Pharmaceuticals Inc; 2018.

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

39. Escudier B, Szczylik C, Hutson TE. 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.

40. Bevacizumab (Avastin) [package insert]. South San Francisco.: Genentech, Inc.; 2018.

41. 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.

42. Irshad T, Olencki T, Zynger DL, et al. Bevacizumab in metastatic papillary renal cell carcinoma (PRCC) [abstract]. J Clin Oncol. 2016;29(suppl_e15158).

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

44. 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 carcinoma (HLRCC) or sporadic papillary renal cell cancer (RCC). J Clin Oncol. 2012;30:(15_suppl_abstr TPS4680).

45. Srinivasin 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. Eur J Cancer. 2014;50(suppl_abstr 5).

46. 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.

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

48. 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.

49. Gangireddy Vg, Liles GB, Sostre GD, et al. Response of metastatic renal medullary carcinoma to carboplatinum and paclitaxel chemotherapy. Clin Genitourin Cancer. 2012;10:134-139.

(Revised 10/2019) © 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
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