Renal cell carcinoma

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 Teja Ganta, MD
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Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page or to a histology- or biomarker-specific page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: This page contains trials that did not specify histology or allowed patients with multiple histologies. Trials limited to a specific histology including those that required a clear-cell component are on dedicated pages:

14 regimens on this page
22 variants on this page


Living Interactive Systematic Reviews

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ESMO

ISRS

NCCN

SIOG

SITC

Risk Stratification Calculators

Adjuvant therapy

Sunitinib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Haas et al. 2016 (ECOG-ACRIN E2805) 2006-2010 Phase 3 (E-esc) 1. Placebo
2. Sorafenib 		Did not meet primary endpoint of DFS

Preceding treatment

Targeted therapy

42-day cycle for up to 9 cycles (1 year)

References

  1. ECOG-ACRIN E2805: Haas NB, Manola J, Uzzo RG, Flaherty KT, Wood CG, Kane C, Jewett M, Dutcher JP, Atkins MB, Pins M, Wilding G, Cella D, Wagner L, Matin S, Kuzel TM, Sexton WJ, Wong YN, Choueiri TK, Pili R, Puzanov I, Kohli M, Stadler W, Carducci M, Coomes R, DiPaola RS. 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 May 14;387(10032):2008-16. Epub 2016 Mar 9. Erratum in: Lancet. 2016 May 14;387(10032):1998. link to original article link to PMC article PubMed NCT00326898

Metastatic disease, first-line

Atezolizumab & Bevacizumab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Rini et al. 2019 (IMmotion151) 2015-05-20 to 2016-10-12 Phase 3 (E-esc) Sunitinib Seems to have superior PFS1 (co-primary endpoint)
Median PFS: 11.2 vs 7.7 mo
(HR 0.74, 95% CI 0.57-0.96)

1Reported efficacy is for the PD-L1-positive subgroup, which was the predefined co-primary endpoint.
Note: patients could have clear cell or sarcomatoid histology.

Immunotherapy

Targeted therapy

21-day cycles

References

  1. IMmotion151: Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. Epub 2019 May 9. link to original article contains dosing details in abstract PubMed NCT02420821
    1. Update: Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Alekseev BY, Lee JL, Suarez C, Stroyakovskiy D, De Giorgi U, Donskov F, Mellado B, Banchereau R, Hamidi H, Khan O, Craine V, Huseni M, Flinn N, Dubey S, Rini BI. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022 Feb 1;8(2):275-280. link to original article [link to PMC article PubMed

Everolimus monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Motzer et al. 2014 (RECORD-3) 2009-2011 Randomized Phase 2 (E-switch-ic) Sunitinib Inconclusive whether non-inferior PFS (primary endpoint)

Targeted therapy

Continued indefinitely

Subsequent treatment

  • RECORD-3, upon progression: Second-line Sunitinib

Dose and schedule modifications

  • Everolimus dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability

References

  1. RECORD-3: Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. link to original article link to PMC article PubMed NCT00903175

Gemcitabine & Sunitinib

Regimen

Study Dates of enrollment Evidence
Michaelson et al. 2015 (MGH 07-212) 2007-2013 Phase 2

Chemotherapy

Targeted therapy

21-day cycles

References

  1. MGH 07-212: Michaelson MD, McKay RR, Werner L, Atkins MB, Van Allen EM, Olivier KM, Song J, Signoretti S, McDermott DF, Choueiri TK. Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Cancer. 2015 Oct 1;121(19):3435-43. Epub 2015 Jun 8. link to original article PubMed NCT00556049

High-dose Interleukin-2

HD IL-2: High-Dose InterLeukin-2

Example orders

Regimen variant #1, 1.8 MU/kg/day, intermittent

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Rosenberg et al. 1994 1985-1992 Non-randomized
Fyfe et al. 1995 NR Phase 2 (RT)
McDermott et al. 2005 1997-2000 Phase 3 (C) Subcutaneous IL-2 & Interferon Might have superior PFS

Immunotherapy

Supportive therapy

28-day cycle for up to 3 cycles


Regimen variant #2, 2.16 MU/kg/day, intermittent, goal 10.8 MU

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Yang et al. 1994 1991-1993 Phase 3 (C) 1. LD IL-2 (IV) Seems to have superior ORR
2. LD IL-2 (SC) Seems to have superior ORR

Note: reported efficacy is based on the 2003 update.

Immunotherapy

8-week cycle for up to 2 cycles


Regimen variant #3, 5 MU/m2/day, CI

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Figlin et al. 1999 1994-1997 Phase 3 (C) IL-2 & CD8+ TILs Did not meet primary endpoint of ORR

Immunotherapy

  • IL-2 - Aldesleukin (Proleukin) 5,000,000 units/m2/day IV continuous infusion over 96 hours, started on days 1, 8, 15, 22 (total dose per cycle: 80 MU/m2)

8-week cycles

References

  1. Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994 Mar 23-30;271(12):907-13. link to original article PubMed
  2. Yang JC, Topalian SL, Parkinson D, Schwartzentruber DJ, Weber JS, Ettinghausen SE, White DE, Steinberg SM, Cole DJ, Kim HI, Levin R, Guleria A, MacFarlane MP, White RL, Einhorn JH, Seipp CA, Rosenberg SA. Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J Clin Oncol. 1994 Aug;12(8):1572-6. link to original article PubMed
    1. Update: Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003 Aug 15;21(16):3127-32. link to original article link to PMC article contains dosing details in manuscript PubMed
  3. Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995 Mar;13(3):688-96. link to original article PubMed
  4. Figlin RA, Thompson JA, Bukowski RM, Vogelzang NJ, Novick AC, Lange P, Steinberg GD, Belldegrun AS. Multicenter, randomized, phase III trial of CD8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol. 1999 Aug;17(8):2521-9. link to original article contains dosing details in manuscript PubMed
  5. McDermott DF, Regan MM, Clark JI, Flaherty LE, Weiss GR, Logan TF, Kirkwood JM, Gordon MS, Sosman JA, Ernstoff MS, Tretter CP, Urba WJ, Smith JW, Margolin KA, Mier JW, Gollob JA, Dutcher JP, Atkins MB. 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 Jan 1;23(1):133-41. link to original article contains dosing details in manuscript PubMed

Low-dose Interleukin-2

LD IL-2: Low-Dose InterLeukin-2

Regimen variant #1, Intravenous

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Yang et al. 1994 1991-1993 Phase 3 (E-de-esc) 1. High-dose IL-2 Seems to have inferior ORR
2. LD IL-2; SC Not reported

Note: efficacy is based on the 2003 update.

Immunotherapy

  • IL-2 - Aldesleukin (Proleukin) as follows:
    • Week 1: 72,000 units/kg IV every 8 hours for up to 15 doses
    • Then after 7 to 10 days of rest: 72,000 units/kg IV every 8 hours for up to 15 doses is given again

8-week cycle for up to 2 cycles


Regimen variant #2, Subcutaneous

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Yang et al. 1994 1991-1993 Phase 3 (E-de-esc) 1. High-dose IL-2 Seems to have inferior ORR
2. LD IL-2; IV Not reported

Note: this arm was added to the trial after the interim results were announced in 1994.

Immunotherapy

  • IL-2 - Aldesleukin (Proleukin) as follows:
    • Week 1: 250,000 units/kg SC once per day for 5 days
    • Weeks 2 to 6: 125,000 units/kg SC once per day for 5 days per week

8-week cycle for up to 2 cycles

References

  1. Yang JC, Topalian SL, Parkinson D, Schwartzentruber DJ, Weber JS, Ettinghausen SE, White DE, Steinberg SM, Cole DJ, Kim HI, Levin R, Guleria A, MacFarlane MP, White RL, Einhorn JH, Seipp CA, Rosenberg SA. Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J Clin Oncol. 1994 Aug;12(8):1572-6. link to original article PubMed
    1. Update: Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003 Aug 15;21(16):3127-32. link to original article link to PMC article contains dosing details in manuscript PubMed

Interferon alfa-2a monotherapy

Regimen variant #1, 5 MU 5x per week

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Sagaster et al. 1995 NR-1992 Phase 3 (C) Cimetidine, Coumarin, IFN alfa-2a Did not meet primary endpoint of ORR

Immunotherapy

7-day cycles


Regimen variant #2, 9 MU TIW

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gore et al. 2010 (MRC RE04/EORTC GU 30012) 2001-2006 Phase 3 (C) 5-FU, Interferon alfa-2a, IL-2 Did not meet primary endpoint of OS
Hawkins et al. 2016 (Active Biotech 06762004) 2007-2010 Phase 2/3 (C) Naptumomab estafenatox + IFNα Did not meet primary endpoint of OS

Immunotherapy

Given for varying lengths of time; see individual trials

Dose and schedule modifications

  • Some protocols: Dose can be reduced to 3,000,000 or 6,000,000 units SC 3 times per week based on tolerability


Regimen variant #3, 9 MU daily, with lead-in

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Motzer et al. 2000 1994-1996 Phase 3 (C) IFN alfa & 13-CRA Did not meet primary endpoint of ORR

Note: Interferon alfa-2a dose was increased only if the prior dose was tolerated.

Immunotherapy

  • Interferon alfa-2a (Roferon-A) as follows:
    • Cycle 1: 3,000,000 units SC once per day on days 1 to 7
    • Cycle 2: 6,000,000 units SC once per day on days 1 to 7
    • Cycle 3 onwards: 9,000,000 units SC once per day on days 1 to 7

7-day cycles


Regimen variant #4, 10 MU TIW, with lead-in

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Ritchie et al. 1999 (MRC RE01) 1992-1997 Phase 3 (E-switch-ooc) MPA Superior OS (primary endpoint)
Median OS: 8.5 vs 6 mo
(HR 0.72, 95% CI 0.55-0.94)

Immunotherapy

  • Interferon alfa-2a (Roferon-A) as follows:
    • Cycle 1: 5,000,000 units SC once per day on days 1 & 3, then 10,000,000 units SC once on day 5
    • Cycles 2 to 12: 10,000,000 units SC once per day on days 1, 3, 5 (3 times per week)

7-day cycle for 12 cycles


Regimen variant #5, 10 MU TIW

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gore et al. 2010 (MRC RE04/EORTC GU 30012) 2001-2006 Phase 3 (C) 5-FU, Interferon alfa-2a, IL-2 Did not meet primary endpoint of OS

Immunotherapy

7-day cycles


Regimen variant #6, 18 MU TIW, with lead-in

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fosså et al. 1992 1985-1986 Phase 3 (C) IFN alfa-2a & Vinblastine Did not meet efficacy endpoints
Hudes et al. 2007 (ARCC) 2003-2005 Phase 3 (C) 1. Interferon alfa-2a & Temsirolimus Did not meet primary endpoint of OS
2. Temsirolimus Inferior OS

Note: Interferon alfa-2a dose was increased only if the prior dose was tolerated.

Immunotherapy

  • Interferon alfa-2a (Roferon-A) as follows:
    • Cycle 1: 3,000,000 units SC once per day on days 1, 3, 5
    • Cycle 2: 9,000,000 units SC once per day on days 1, 3, 5
    • Cycle 3 onwards: 18,000,000 units SC once per day on days 1, 3, 5

7-day cycles

Dose and schedule modifications

  • If higher doses cannot be tolerated, highest tolerable doses of 3,000,000, 4,500,500, or 6,000,000 units can be used

References

  1. Fosså SD, Martinelli G, Otto U, Schneider G, Wander H, Oberling F, Bauer HW, Achtnicht U, Holdener EE. Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study. Ann Oncol. 1992 Apr;3(4):301-5. link to original article PubMed
  2. Sagaster P, Micksche M, Flamm J, Ludwig H. Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer. Ann Oncol. 1995 Dec;6(10):999-1003. link to original article contains dosing details in abstract PubMed
  3. MRC RE01: Ritchie A, Griffiths G, Parmar M; Medical Research Council Renal Cancer Collaborators. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Lancet. 1999 Jan 2;353(9146):14-7. link to original article contains dosing details in abstract PubMed
  4. Motzer RJ, Murphy BA, Bacik J, Schwartz LH, Nanus DM, Mariani T, Loehrer P, Wilding G, Fairclough DL, Cella D, Mazumdar M. Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol. 2000 Aug;18(16):2972-80. link to original article PubMed
  5. ARCC: Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. link to original article contains dosing details in manuscript PubMed NCT00065468
  6. MRC RE04/EORTC GU 30012: Gore ME, Griffin CL, Hancock B, Patel PM, Pyle L, Aitchison M, James N, Oliver RT, Mardiak J, Hussain T, Sylvester R, Parmar MK, Royston P, Mulders PF. Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial. Lancet. 2010 Feb 20;375(9715):641-8. Epub 2010 Feb 10. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00053820
  7. Active Biotech 06762004: Hawkins RE, Gore M, Shparyk Y, Bondar V, Gladkov O, Ganev T, Harza M, Polenkov S, Bondarenko I, Karlov P, Karyakin O, Khasanov R, Hedlund G, Forsberg G, Nordle Ö, Eisen T. A randomized phase II/III study of naptumomab estafenatox + IFNα versus IFNα in renal cell carcinoma: final analysis with baseline biomarker subgroup and trend analysis. Clin Cancer Res. 2016 Jul 1;22(13):3172-81. Epub 2016 Feb 5. link to original article contains dosing details in manuscript PubMed NCT00420888

Sorafenib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Stadler et al. 2010 (ARCCS) 2005-06 to 2006-07 Non-randomized
Retz et al. 2018 (SWITCH-II) 2012-06-14 to 2016-11-14 Phase 3 (C) Pazopanib Inconclusive whether non-inferior tPFS

Targeted therapy

Continued indefinitely

Dose and schedule modifications

  • Sorafenib can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity

Subsequent treatment

References

  1. ARCCS: Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Bukowski RM; ARCCS Study Investigators. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. 2010 Mar 1;116(5):1272-80. link to original article PubMed NCT00111020
  2. SWITCH-II: Retz M, Bedke J, Bögemann M, Grimm MO, Zimmermann U, Müller L, Leiber C, Teber D, Wirth M, Bolenz C, van Alphen R, De Santis M, Beeker A, Lehmann J, Indorf M, Frank M, Bokemeyer C, Gschwend JE. SWITCH II: Phase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of advanced or metastatic renal cell carcinoma (AUO AN 33/11). Eur J Cancer. 2019 Jan;107:37-45. Epub 2018 Dec 7. link to original article contains dosing details in abstract PubMed NCT01613846

Sunitinib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gore et al. 2009 (A618-1037) 2005-2007 Non-randomized
Motzer et al. 2014 (RECORD-3) 2009-2011 Randomized Phase 2 (E-switch-ic) Everolimus Inconclusive whether non-inferior PFS (primary endpoint)
Eichelberg et al. 2015 (SWITCH) 2009-2011 Phase 3 (C) Sorafenib Did not meet primary endpoint of PFS
Rini et al. 2019 (IMmotion151) 2015-05-20 to 2016-10-12 Phase 3 (C) Atezolizumab & Bevacizumab Seems to have inferior PFS

Targeted therapy

42-day cycles

Subsequent treatment

  • SWITCH, upon progression: Second-line Sorafenib

Dose and schedule modifications

  • Per some references, dose may be decreased to 37.5 mg or 25 mg PO once per day depending on tolerability

References

  1. A618-1037: Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schöffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009 Aug;10(8):757-63. Epub 2009 Jul 15. link to original article contains dosing details in manuscript PubMed NCT00130897
  2. PISCES: Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, Gschwend JE, De Giorgi U, Parikh O, Hawkins R, Sevin E, Négrier S, Khan S, Diaz J, Redhu S, Mehmud F, Cella D. 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 May 10;32(14):1412-8. Epub 2014 Mar 31. link to original article PubMed NCT01064310
  3. RECORD-3: Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. link to original article link to PMC article PubMed NCT00903175
  4. SWITCH: Eichelberg C, Vervenne WL, De Santis M, Fischer von Weikersthal L, Goebell PJ, Lerchenmüller C, Zimmermann U, Bos MM, Freier W, Schirrmacher-Memmel S, Staehler M, Pahernik S, Los M, Schenck M, Flörcken A, van Arkel C, Hauswald K, Indorf M, Gottstein D, Michel MS. SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer. Eur Urol. 2015 Nov;68(5):837-47. Epub 2015 May 4. link to original article contains dosing details in abstract PubMed NCT00732914
  5. IMmotion151: Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. Epub 2019 May 9. link to original article contains dosing details in abstract PubMed NCT02420821
    1. Update: Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Alekseev BY, Lee JL, Suarez C, Stroyakovskiy D, De Giorgi U, Donskov F, Mellado B, Banchereau R, Hamidi H, Khan O, Craine V, Huseni M, Flinn N, Dubey S, Rini BI. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022 Feb 1;8(2):275-280. link to original article [link to PMC article PubMed

Temsirolimus monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hudes et al. 2007 (ARCC) 2003-2005 Phase 3 (E-RT-switch-ooc) 1. Interferon alfa-2a Superior OS (primary endpoint)
Median OS: 10.9 vs 7.3 mo
(HR 0.73, 95% CI 0.58-0.92)
2. Interferon alfa-2a & Temsirolimus Not reported

Targeted therapy

Supportive therapy

7-day cycles

References

  1. ARCC: Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. link to original article contains dosing details in manuscript PubMed NCT00065468

Metastatic disease, second-line

Cabozantinib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pal et al. 2023 (CONTACT-03) 2020-07-28 to 2021-12-27 Phase 3 (C) Cabozantinib & Atezolizumab Did not meet co-primary endpoints of PFS/OS

Targeted therapy

28-day cycles

References

  1. CONTACT-03: Pal SK, Albiges L, Tomczak P, Suárez C, Voss MH, de Velasco G, Chahoud J, Mochalova A, Procopio G, Mahammedi H, Zengerling F, Kim C, Osawa T, Angel M, Gupta S, Khan O, Bergthold G, Liu B, Kalaitzidou M, Huseni M, Scheffold C, Powles T, Choueiri TK. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2023 Jul 15;402(10397):185-195. Epub 2023 Jun 5. link to original article contains dosing details in abstract PubMed NCT04338269

Everolimus monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Motzer et al. 2014 (RECORD-3) 2009-2011 Randomized Phase 2 (E-switch-ic) Sunitinib Inconclusive whether non-inferior PFS (primary endpoint)

Prior treatment criteria

Targeted therapy

Continued indefinitely

Dose and schedule modifications

  • Everolimus dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability

References

  1. RECORD-3: Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. link to original article link to PMC article PubMed NCT00903175

Sorafenib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Stadler et al. 2010 (ARCCS) 2005-06 to 2006-07 Non-randomized expanded access study
Beck et al. 2011 (EU-ARCCS) 2005-2007 Non-randomized expanded access study
Hutson et al. 2013 (INTORSECT) 2007-2011 Phase 3 (C) Temsirolimus Did not meet primary endpoint of PFS2
Median PFS: 3.9 vs 4.3 mo
(HR 1.15, 95% CI 0.93-1.41)

1Reported efficacy for TARGET is based on the 2009 update.
2While the primary endpoint (PFS) was not met in INTORSECT, the control arm actually had superior OS compared to the experimental arm.

Prior treatment criteria

  • INTORSECT: Sunitinib, with progression

Targeted therapy

Continued indefinitely

Dose and schedule modifications

  • Sorafenib can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity

References

  1. ARCCS: Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Bukowski RM; ARCCS Study Investigators. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. 2010 Mar 1;116(5):1272-80. link to original article PubMed NCT00111020
  2. EU-ARCCS: Beck J, Procopio G, Bajetta E, Keilholz U, Negrier S, Szczylik C, Bokemeyer C, Bracarda S, Richel DJ, Staehler M, Strauss UP, Mersmann S, Burock K, Escudier B. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann Oncol. 2011 Aug;22(8):1812-23. Epub 2011 Feb 15. link to original article contains dosing details in manuscript PubMed
  3. INTORSECT: Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, Senico P, Niethammer A, Lu DR, Hariharan S, Motzer RJ. Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Mar 10;32(8):760-7. Epub 2013 Dec 2. link to original article contains dosing details in abstract link to PMC article PubMed NCT00474786

Sunitinib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Motzer et al. 2005 (RTKC-0511-014) 2003 Phase 2 (RT)
Gore et al. 2009 (A618-1037) 2005-2007 Non-randomized
Motzer et al. 2014 (RECORD-3) 2009-2011 Randomized Phase 2 (E-switch-ic) Everolimus Inconclusive whether non-inferior PFS (primary endpoint)

Preceding treatment

Targeted therapy

42-day cycles

Dose and schedule modifications

  • Dose may be decreased to 37.5 mg or 25 mg PO once per day depending on tolerability

References

  1. RTKC-0511-014: Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Ginsberg MS, Kim ST, Baum CM, DePrimo SE, Li JZ, Bello CL, Theuer CP, George DJ, Rini BI. 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 Jan 1;24(1):16-24. Epub 2005 Dec 5. link to original article PubMed
  2. A618-1037: Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schöffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009 Aug;10(8):757-63. Epub 2009 Jul 15. link to original article contains dosing details in manuscript PubMed NCT00130897
  3. RECORD-3: Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. link to original article link to PMC article PubMed NCT00903175
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