Kidney Cancer Treatment Regimens

Kidney Cancer 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.


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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 Grade 4 Tumors With Clear Cell Histology +/- Sarcomatoid Features1

REGIMEN

DOSING

Stage II Disease

Pembrolizumab2-5

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for 17 cycles.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for 1 year.

▶Adjuvant Therapy for Patients With Clear Cell Histology1

Stage III Disease

Pembrolizumab2-5

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for 17 cycles.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for 1 year.

Sunitinib (Category 3)6-10

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

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

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

Favorable Risk

Preferred Regimens

Axitinib + Pembrolizumab (Category  1)2,5,11,12,b

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years, concurrent with:

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

Repeat cycle every 4 weeks.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years, concurrent with:

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

Repeat cycle every 4 weeks.

Cabozantinib + Nivolumab (Category 1)13-15,c

Days 1-28: Cabozantinib 40mg orally once daily.

Day 1 and 15: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 4 weeks for up to 2 years, conditionally followed by:

Days 1-28: Cabozantinib 40mg orally daily.

Repeat cycle every 4 weeks.

OR

Days 1-28: Cabozantinib 40mg orally once daily.

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks for up to 2 years, conditionally followed by:

Days 1-28: Cabozantinib 40mg orally daily.

Repeat cycle every 4 weeks.

Lenvatinib + Pembrolizumab (Category 1)2,16-18

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years, concurrent with:

Days 1-21: Lenvatinib 20mg orally once daily.

Repeat cycle every 3 weeks.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years, concurrent with:

Days 1-42: Lenvatinib 20mg orally once daily.

Repeat cycle every 6 weeks.

Other Recommended Regimens

Axitinib + Avelumab11,19,20,b

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

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

Repeat cycle every 4 weeks.

Cabozantinib (Category 2B)13,21-23,c

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

Repeat cycle every 4 weeks.

Nivolumab + Ipilimumab Followed by Nivolumab15,24-27

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

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, followed by:

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.

Pazopanib28-32

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

Repeat cycle every 4 weeks.

Sunitinib6-10

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)11,33-35,b

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

Repeat cycle every 4 weeks.

High-dose Aldesleukin (Interleukin-2) (Category 2B)36,37,d

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

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

Poor/Intermediate Risk

Preferred Regimens

Axitinib + Pembrolizumab (Category 1)2,5,11,12,b

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years, concurrent with:

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

Repeat cycle every 4 weeks.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years, concurrent with:

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

Repeat cycle every 4 weeks.

Cabozantinib13,21-23,c

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

Repeat cycle every 4 weeks.

Cabozantinib + Nivolumab (Category 1)13-15,c

Days 1-28: Cabozantinib 40mg orally once daily.

Day 1 and 15: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 4 weeks for up to 2 years, conditionally followed by:

Days 1-28: Cabozantinib 40mg orally daily.

Repeat cycle every 4 weeks.

OR

Days 1-28: Cabozantinib 40mg orally once daily.

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks for up to 2 years, conditionally followed by:

Days 1-28: Cabozantinib 40mg orally daily.

Repeat cycle every 4 weeks.

Lenvatinib + Pembrolizumab (Category 1)2,16-18

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years, concurrent with:

Days 1-21: Lenvatinib 20mg orally once daily.

Repeat cycle every 3 weeks.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years, concurrent with:

Days 1-42: Lenvatinib 20mg orally once daily.

Repeat cycle every 6 weeks.

Nivolumab + Ipilimumab Followed by Nivolumab (Category 1)14,21-27

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

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, followed by:

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 + Avelumab11,19,20,b

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

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

Repeat cycle every 4 weeks.

Pazopanib28-32

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

Repeat cycle every 4 weeks.

Sunitinib6-10

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)11,33-35,b

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

Repeat cycle every 4 weeks.

High-dose Aldesleukin (Interleukin-2) (Category 3)36,37,d

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

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

Temsirolimus (Category 3)38-40

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)13,21-23,c

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

Repeat cycle every 4 weeks.

Lenvatinib + Everolimus (Category 1)16,41,42

Days 1-28: Everolimus 5mg orally once daily

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

Repeat cycle every 4 weeks.

Nivolumab (Category 1)15,43-45

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)11,33-35,b

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

Repeat cycle every 4 weeks.

Axitinib + Avelumab (Category 3)11,33-35,b

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 + Pembrolizumab2,5,11,12,b

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years, concurrent with:

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

Repeat cycle every 4 weeks.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years, concurrent with:

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

Repeat cycle every 4 weeks.

Cabozantinib + Nivolumab13-15,c

Days 1-28: Cabozantinib 40mg orally once daily.

Day 1 and 15: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 4 weeks for up to 2 years, conditionally followed by:

Days 1-28: Cabozantinib 40mg orally daily.

Repeat cycle every 4 weeks.

OR

Days 1-28: Cabozantinib 40mg orally once daily.

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks for up to 2 years, conditionally followed by:

Days 1-28: Cabozantinib 40mg orally daily.

Repeat cycle every 4 weeks.

Lenvatinib + Pembrolizumab2,16-18

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years, concurrent with:

Days 1-21: Lenvatinib 20mg orally once daily.

Repeat cycle every 3 weeks.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years, concurrent with:

Days 1-42: Lenvatinib 20mg orally once daily.

Repeat cycle every 6 weeks.

Nivolumab + Ipilimumab Followed by Nivolumab14,24-27

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

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, followed by:

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.

Pazopanib28-32

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

Repeat cycle every 4 weeks.

Sunitinib6-10

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

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

Tivozanib46-48

Days 1-21: Tivozanib 1.34mg orally once daily.

Repeat cycle every 4 weeks.

Useful Under Certain Circumstances

Bevacizumab (Category 2B)49-51,e

Day 1: Bevacizumab 10mg/kg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Everolimus41,52-54

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

Repeat cycle every 4 weeks.

High-dose Aldesleukin (Interleukin-2) (Category 2B)36,37,d

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

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

Sorafenib (Category 3)55-57

Days 1-28: Sorafenib 400mg orally twice daily. Repeat cycle every 4 weeks.

Temsirolimus (Category 2B)38-40

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

Cabozantinib13,21-23,c

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

Repeat cycle every 4 weeks.

Sunitinib6-10

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

Lenvatinib + Everolimus16,41,42

Days 1-28: Everolimus 5mg orally once daily

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

Repeat cycle every 4 weeks.

Nivolumab124,43-45

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.

Pembrolizumab2-5

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks for up to 2 years.

Useful Under Certain Circumstances

Axitinib11,32-34,b

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

Repeat cycle every 4 weeks.

Bevacizumab49-51,e

Day 1: Bevacizumab 10mg/kg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Doxorubicin/Gemcitabine (for renal medullary carcinoma)58-60,f

Day 1: Doxorubicin 50mg/m2 IV push.

Day 1: Gemcitabine 1,500mg/m2 IV over 30 minutes.

Repeat cycle every 2 weeks.

Erlotinib61,62

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

Repeat cycle every 4 weeks.

Erlotinib + Bevacizumab49,61,63,64

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

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

Repeat cycle every 4 weeks.

Everolimus41,52-54

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

Repeat cycle every 4 weeks.

Everolimus + Bevacizumab (for selected patients with advanced papillary renal cell carcinoma)41,49,65,e

Days 1-28: Everolimus 10mg orally once daily

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

Repeat cycle every 4 weeks.

Gemcitabine/Carboplatin (for patients with collecting duct or medullary subtypes)59,66,67

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)59,67,68,g

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

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

Repeat cycle every 3 weeks for 6 cycles.

Paclitaxel/ Carboplatin (for patients with collecting duct or medullary subtypes)68-70

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

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

Repeat cycle every 3 weeks for 6 cycles.

Pazopanib28-32

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)38-40

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

Repeat cycle weekly.

▶Kidney-Specific Systemic Therapy for Confirmed Hereditary Renal Cell Carcinoma1

Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC)

Useful Under Certain Circumstances

Erlotinib + Bevacizumab49,61,63,64

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

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

Repeat cycle every 4 weeks.

Tuberous Sclerosis Complex (TSC)

Useful Under Certain Circumstances

Everolimus41,52-54

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

Repeat cycle every 4 weeks.

von Hippel-Lindau Disease (VHL)

Preferred Regimen

Belzutifan71,72

Days 1-28: Belzutifan 120mg orally once daily.

Repeat cycle every 4 weeks.

Useful Under Certain Circumstances

Pazopanib28-32

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

Repeat cycle every 4 weeks.

a Adjuvant pembrolizumab (200mg IV over 30 minutes, repeat cycle every 3 weeks for up to 2 years OR 400mg IV over 30 minutes, repeat cycle every 6 weeks for up to 2 years)2-5 after metastasectomy within 1 year of nephrectomy is an option for patients with disease characterized by clear cell histology.

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 Cabozantinib (Cabometyx®) tablets and cabozantinib (Cometriq®) capsules are not interchangeable products. The dosage strengths of each product and dosing recommendations for specific indications differ.

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

e An FDA-approved biosimilar is an appropriate substitute for bevacizumab.

f Doxorubicin is an anthracycline. Cumulative anthracycline dosage should be monitored.

g Hydration is required with supplemental electrolytes pre- and post-administration of Cisplatin.

References

 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology® Kidney Cancer v4.2022. https://www.nccn.org/professionals/physician_gls/pdf/ kidney.pdf. Accessed January 14, 2022.

 2. Pembrolizumab (Keytruda). [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; August, 2021.

 ;3. McDermott DF, Lee JL, Ziobro M, et al. Open-label, single-arm, phase II study of pembrolizumab monotherapy as first-line therapy in patients with advanced non-clear cell renal cell carcinoma. J Clin Oncol. 2021;39:1029-1039.

 4. Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385(8):683-694.

 5. Lala M, Li TR, de Alwis DP, et al. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. Eur J Cancer. 2020;131:68-75.

 6. Sunitinib (Sutent) [package insert]. New York, NY: Pfizer Inc.; August, 2021.

 7. 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.

 8. 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.

 9. 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.

10. 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.

11. Axitinib (Inlyta) [package insert]. New York, NY: Pfizer, Inc.; June, 2020.

12. 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.

13. Cabozantinib (Cabometryx) [package insert]. Alameda, CA: Exelixis, Inc; September, 2021.

14. Nivolumab (Opdivo) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.; August, 2021.

15. Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384:829-841.

16. Lenvatinib (Lenvima) [package insert]. Woodcliff Lake, NJ: Eisai Inc.; August, 2021.

17. Taylor MH, Lee CH, Makker V, et al. Phase IB/II trial of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma, endometrial cancer, and other selected advanced solid tumors. J Clin Oncol. 2020;38:1154-1163.

18. Lee CH, Shah AY, Rasco D, et al. Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (study 111/KEYNOTE-146): a phase 1b/2 study. Lancet Oncol. 2021;22:946-958.

19. Avelumab (Bavencio) [package insert]. Rockland, MA: EMD Serono, Inc.; November, 2020.

20. 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.

21. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17:917-927.

22. 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.

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

24. Ipilimumab (Yervoy). [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; May, 2021.

25. 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.

26. 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.

27. Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 2019;20:1370-1385.

28. Pazopanib (Votrient) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2017.

29. 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.

30. 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.

31. 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).

32. Jonasch E, McCutcheon IE, Gombos DS, et al. Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single-centre, phase 2 trial. Lancet Oncol. 2018;19:1351-1359.

33. 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.

34. 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.

35. 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.

36. Aldesleukin (Proleukin) [package insert]. San DiegoPrometheus Laboratories, Inc.; May, 2019.

37. 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.

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

39. 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.

40. 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.

41. Everolimus (Afinitor) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; April, 2021.

42. 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.

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

44. 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.

45. Koshkin VS, Barata PC, Zhang T, et al. Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma. J Immunother Cancer. 2018;6:9.

46. Tivozanib (Fotivda) [package insert]. Boston, MA: AVEO Pharmaceuticals, Inc.; March, 2021.

47. Rini BI, Pal SK, Escudier BJ. et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020;21:95-104.

48. Pal SK, Escudier BJ, Atkins MB, et al. Final overall survival results from a phase 3 study to compare tivozanib to sorafenib as third- or fourth-line therapy in subjects with metastatic renal cell carcinoma. Eur Urol. 2020;78:783-785.

49. Bevacizumab (Avastin) [package insert]. South San Francisco.: Genentech, Inc.; December, 2020.

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(Revised 1/2022; NCCN Clinical Practice Guidelines in Oncology® Kidney Cancer v4.2022) © 2022 by Haymarket Media, Inc.

This article originally appeared on Cancer Therapy Advisor