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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:

Histology-specific:
- Clear cell renal cell carcinoma
- Non-clear cell renal cell carcinoma
  - Papillary renal cell carcinoma
  - Sarcomatoid renal cell carcinoma
Biomarker-specific:
- RCC, VHL-associated

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

2021: Kanesveran et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma PubMed
2021: Powles et al. ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma PubMed
2019: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2016: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2014: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2012: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Escudier & Kataja. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Escudier & Kataja. Renal cell carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed

ISRS

2024: Siva et al. Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS) PubMed

NCCN

NCCN Guidelines - Kidney Cancer
2022: Motzer et al. Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. PubMed
2017: Motzer et al. Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology PubMed
2015: Motzer et al. Kidney Cancer, Version 3.2015 PubMed
2014: Motzer et al. Kidney cancer, version 2.2014 PubMed
2011: Motzer et al. Kidney cancer. PubMed
2009: Motzer et al. NCCN clinical practice guidelines in oncology: kidney cancer. PubMed
2006: Motzer et al. Kidney cancer. Clinical practice guidelines in oncology. PubMed
2005: Motzer et al. Kidney cancer. Clinical practice guidelines. PubMed

SIOG

2018: Kanesvaran et al. Elderly patients with metastatic renal cell carcinoma: position paper from the International Society of Geriatric Oncology PubMed

SITC

2019: Rini et al. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC) PubMed

Risk Stratification Calculators

International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) calculator
- ref: Heng DY, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN, Mackenzie M, Wood L, Donskov F, Tan MH, Rha SY, Agarwal N, Kollmannsberger C, Rini BI, Choueiri TK; External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013 Feb;14(2):141-8. Epub 2013 Jan 9. link to PMC article PubMed
Memorial Sloan Kettering Cancer Center (MSKCC) calculator
- ref: Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002 Jan 1;20(1):289-96. link to original article PubMed
Mortality and complication risk calculator for a patients with clinical T1 renal cortical mass up to 7 cm (Dr. Sarah P. Psutka)
- ref: Psutka SP et al., A clinical decision aid to support personalized treatment selection for patients with stage T1 renal masses: Results from a multi-institutional competing risks analysis including performance status and comorbidity. Working paper. link to news article
UCLA Integrated Staging System (UISS) for Renal Cell Carcinoma (RCC)
- ref: Zisman A, Pantuck AJ, Dorey F, Said JW, Shvarts O, Quintana D, Gitlitz BJ, deKernion JB, Figlin RA, Belldegrun AS. Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol. 2001 Mar 15;19(6):1649-57. PubMed
Leibovich prognostic model
- ref: Leibovich BC, Lohse CM, Cheville JC, Zaid HB, Boorjian SA, Frank I, Thompson RH, Parker WP. Predicting Oncologic Outcomes in Renal Cell Carcinoma After Surgery. Eur Urol. 2018 May;73(5):772-780. Epub 2018 Feb 3. PubMed

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

Surgery

Targeted therapy

Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28

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

References

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

Atezolizumab (Tecentriq) 1200 mg IV once on day 1

Targeted therapy

Bevacizumab (Avastin) 15 mg/kg IV once on day 1

21-day cycles

References

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

Everolimus (Afinitor) 10 mg PO once per day

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

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

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8

Targeted therapy

Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 14

21-day cycles

References

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

Example orders for High-dose (HD) IL-2 in renal cancer

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

IL-2 - Aldesleukin (Proleukin) 600,000 units/kg IV every 8 hours for up to 14 doses per week, on days 1 to 5, 15 to 19

Supportive therapy

Ciprofloxacin (Cipro) 250 mg PO twice per day on days 1 to 10, 15 to 24
All antihypertensive therapy discontinued at least 24 hours before each cycle
Acetaminophen (Tylenol) 650 mg PO every 4 hours
Indomethacin (Indocin) 25 mg PO every 6 hours
Ranitidine (Zantac) 150 mg PO or Famotidine (Pepcid) 20 mg PO every 12 hours
Hydroxyzine (Atarax) 25 to 50 mg PO every 6 hours or Diphenhydramine (Benadryl) 25 mg PO every (note: frequency was blank in reference) hours for pruritis
Meperidine (Demerol) 25 to 50 mg PO every 6 hours for chills and rigors
"An antidiarrheal agent, antiemetics, anxiolytics, diuretics, and vasopressors as needed"

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
Yang et al. 1994	1991-1993	Phase 3 (C)	2. LD IL-2 (SC)	Seems to have superior ORR

Note: reported efficacy is based on the 2003 update.

Immunotherapy

IL-2 - Aldesleukin (Proleukin) 720,000 units/kg IV every 8 hours for up to 15 doses
- Then after 7 to 10 days of rest, IL-2 - Aldesleukin (Proleukin) 720,000 units/kg IV every 8 hours for up to 15 doses is given again

8-week cycle for up to 2 cycles

Regimen variant #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

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
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
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
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
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
Yang et al. 1994	1991-1993	Phase 3 (E-de-esc)	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
Yang et al. 1994	1991-1993	Phase 3 (E-de-esc)	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

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

Interferon alfa-2a (Roferon-A) 5,000,000 units SC once per day on days 1 to 5 (5 times per week)

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

Interferon alfa-2a (Roferon-A) 9,000,000 units SC 3 times per week

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

Interferon alfa-2a (Roferon-A) 10,000,000 units SC once per day on days 1, 3, 5 (3 times per week)

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
Hudes et al. 2007 (ARCC)	2003-2005	Phase 3 (C)	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

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
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
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
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
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
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
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

Sorafenib (Nexavar) 400 mg PO twice per day

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

SWITCH-II, upon progression: Pazopanib

References

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
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

Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28

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

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
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
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
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
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)
Hudes et al. 2007 (ARCC)	2003-2005	Phase 3 (E-RT-switch-ooc)	2. Interferon alfa-2a & Temsirolimus	Not reported

Targeted therapy

Temsirolimus (Torisel) 25 mg IV over 30 minutes once on day 1

Supportive therapy

Diphenhydramine (Benadryl) (or similar H1 blocker) 25 to 50 mg IV once on day 1; 30 minutes prior to temsirolimus

7-day cycles

References

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

Cabozantinib (Cabometyx) 60 mg PO once per day on days 1 to 28, taken at least 2 hours before or 1 hour after meals

28-day cycles

References

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

RECORD-3: Sunitinib, with progression

Targeted therapy

Everolimus (Afinitor) 10 mg PO once per day

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

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

Sorafenib (Nexavar) 400 mg PO twice per day

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

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
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
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

RECORD-3: First-line Everolimus

Targeted therapy

Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28

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

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
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
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

@@ Line 4: / Line 4: @@
 </div>
 {{#lst:Editorial board transclusions|rcc}}
-''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Renal_cell_carcinoma_-_historical|historical regimens page]] or to a histology- or biomarker-specific page. For placebo or observational studies in this condition, please visit [[Renal cell carcinoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''
+''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Renal_cell_carcinoma_-_historical|historical regimens page]] or to a histology- or biomarker-specific page. For placebo or observational studies in this condition, please visit [[Renal cell carcinoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''<br>
-<br><big>'''There are several related dedicated pages:'''
+'''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:'''
 *'''Histology-specific:'''
 **'''[[Clear cell renal cell carcinoma]]'''
@@ Line 13: / Line 13: @@
 *'''Biomarker-specific:'''
 **'''[[Renal_cell_carcinoma,_VHL-associated|RCC, VHL-associated]]'''
-</big>
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 25: / Line 24: @@
 =Guidelines=
-'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any article published 5+ years ago to be for historical purposes, only.'''
+'''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.'''
-==[http://www.esmo.org/ ESMO]==
+==[https://www.esmo.org/ ESMO]==
-*'''2021:''' Kanesveran et al. [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8645910/ Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma] [https://pubmed.ncbi.nlm.nih.gov/34864348/ PubMed]
+*'''2021:''' Kanesveran et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8645910/ Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma] [https://pubmed.ncbi.nlm.nih.gov/34864348/ PubMed]
 *'''2021:''' Powles et al. [https://doi.org/10.1016/j.annonc.2021.09.014 ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma] [https://pubmed.ncbi.nlm.nih.gov/34597799/ PubMed]
 *'''2019:''' Escudier et al. [https://doi.org/10.1093/annonc/mdz056 Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/30788497/ PubMed]
@@ Line 36: / Line 35: @@
 **'''2009:''' Escudier & Kataja. [https://doi.org/10.1093/annonc/mdp137 Renal cell carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454473/ PubMed]
-==[https://www.nccn.org/ NCCN]==
+==ISRS==
-*[https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf NCCN Guidelines - Kidney Cancer]
+*'''2024:''' Siva et al. [https://doi.org/10.1016/s1470-2045(23)00513-2 Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS)] [https://pubmed.ncbi.nlm.nih.gov/38181809/ PubMed]
+==NCCN==
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1440 NCCN Guidelines - Kidney Cancer]
 *'''2022:''' Motzer et al. [https://doi.org/10.6004/Jnccn.2022.0001 Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/34991070/ PubMed]
 *'''2017:''' Motzer et al. [https://doi.org/10.6004/jnccn.2017.0100 Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology] [https://pubmed.ncbi.nlm.nih.gov/28596261/ PubMed]
@@ Line 50: / Line 52: @@
 *'''2018:''' Kanesvaran et al. [https://doi.org/10.1016/S1470-2045(18)30125-6 Elderly patients with metastatic renal cell carcinoma: position paper from the International Society of Geriatric Oncology] [https://pubmed.ncbi.nlm.nih.gov/29893263/ PubMed]
 ==SITC==
-*'''2019:''' Rini et al. [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6924043/ The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC)] [https://pubmed.ncbi.nlm.nih.gov/31856918/ PubMed]
+*'''2019:''' Rini et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6924043/ The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC)] [https://pubmed.ncbi.nlm.nih.gov/31856918/ PubMed]
 =Risk Stratification Calculators=
@@ Line 69: / Line 71: @@
 ===Regimen {{#subobject:3c0a01|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 17%" |Study
+! style="width: 20%" |Study
-! style="width: 15%" |Dates of enrollment
+! style="width: 20%" |Dates of enrollment
-! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 17%" |Comparator
+! style="width: 20%" |Comparator
-! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878938/ Haas et al. 2016 (ECOG-ACRIN E2805)]
@@ Line 81: / Line 82: @@
 |1. [[Renal_cell_carcinoma_-_null_regimens#Placebo|Placebo]]<br>2. [[#Sorafenib_monotherapy_999|Sorafenib]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
-|
-|-
-|[https://doi.org/10.1056/NEJMoa1611406 Ravaud et al. 2016 (S-TRAC)]
-|2007-2011
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[Renal_cell_carcinoma_-_null_regimens#Placebo|Placebo]]
-| style="background-color:#91cf60" |Seems to have superior DFS (primary endpoint)<br>Median DFS: 6.8 vs 5.6 yr<br>(HR 0.76, 95% CI 0.59-0.98)
-| style="background-color:#d73027" |More toxicity
 |-
 |}
@@ Line 102: / Line 95: @@
 ===References===
 #'''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. [https://doi.org/10.1016/S0140-6736(16)00559-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878938/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26969090/ PubMed] [https://clinicaltrials.gov/study/NCT00326898 NCT00326898]
-#'''S-TRAC:''' Ravaud A, Motzer RJ, Pandha HS, George DJ, Pantuck AJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Martini JF, Ramaswamy K, Casey M, Staehler M, Patard JJ; S-TRAC Investigators. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. 2016 Dec 8;375(23):2246-2254. Epub 2016 Oct 9. [https://doi.org/10.1056/NEJMoa1611406 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27718781/ PubMed] [https://clinicaltrials.gov/study/NCT00375674 NCT00375674]
-##'''Update:''' Motzer RJ, Ravaud A, Patard JJ, Pandha HS, George DJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Casey M, Serfass L, Pantuck AJ, Staehler M. Adjuvant sunitinib for high-risk renal cell carcinoma after nephrectomy: subgroup analyses and updated overall survival results. Eur Urol. 2018 Jan;73(1):62-68. Epub 2017 Sep 26. [https://doi.org/10.1016/j.eururo.2017.09.008 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6684251/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28967554/ PubMed]
 =Metastatic disease, first-line=
 ==Atezolizumab & Bevacizumab {{#subobject:af0d04|Regimen=1}}==
@@ Line 135: / Line 126: @@
 ##'''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. [https://doi.org/10.1001/jamaoncol.2021.5981 link to original article] [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855230/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34940781/ PubMed]
-==Bevacizumab monotherapy {{#subobject:29beb2|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:433717|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.2007.11.5154 Bukowski et al. 2007]
-|2004
-| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[[#Erlotinib_.26_Bevacizumab|Erlotinib & Bevacizumab]]
-| style="background-color:#ffffbf" |Did not meet co-primary endpoints of ORR/PFS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-==== Targeted therapy ====
-*[[Bevacizumab (Avastin)]] 10 mg/kg IV over 90 minutes once on day 1
-'''14-day cycle for up to 52 cycles (2 years)'''
-</div>
-<div class="toccolours" style="background-color:#fff2ae">
-====Dose and schedule modifications====
-*Bevacizumab infusion time can subsequently be reduced to 60 and 30 minute infusions as tolerated
-</div></div>
-===References===
-#Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, Drabkin HA, Dutcher J, Ryba S, Xia Q, Scappaticci FA, McDermott D. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. 2007 Oct 10;25(29):4536-41. Epub 2007 Sep 17. [https://doi.org/10.1200/jco.2007.11.5154 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17876014/ PubMed]
-==Bevacizumab & Interferon alfa-2a {{#subobject:808d58|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 1 year of interferon {{#subobject:dbebac|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1016/S0140-6736(07)61904-7 Escudier et al. 2007 (AVOREN)]
-<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-110-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
-|-
-|} -->
-|2004-06 to 2005-10
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup><br>Median OS: 23.3 vs 21.3 mo<br>(HR 0.91, 95% CI 0.76-1.10)<br><br>Superior PFS<sup>2</sup> (secondary endpoint)<br>Median PFS: 10.2 vs 5.4 mo<br>(HR 0.63, 95% CI 0.52-0.75)
-|-
-|}
-''<sup>1</sup>Reported efficacy for AVOREN is based on the 2010 update.''<br>
-''<sup>2</sup>The secondary endpoint of PFS was used in the FDA regulatory decision; please see paper for details.''<br>
-''Note: Timing below reflects starting treatment on a Monday.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
-====Immunotherapy====
-*[[Interferon alfa-2a (Roferon-A)]] as follows:
-**Cycles 1 to 26: 9,000,000 units SC once per day on days 1, 3, 5, 8, 10, 12 (3 times per week)
-'''14-day cycles'''
-</div>
-<div class="toccolours" style="background-color:#fff2ae">
-====Dose and schedule modifications====
-*[[Interferon alfa-2a (Roferon-A)]] dose can be reduced to 3,000,000 or 6,000,000 units SC 3 times per week based on tolerability
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, indefinite {{#subobject:d136cc|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651074/ Rini et al. 2008 (CALGB 90206)]
-|2003-2005
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]]
-| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 18.3 vs 17.4 mo<br>(HR 0.86, 95% CI 0.73-1.01)
-|-
-|[https://doi.org/10.1200/JCO.2013.50.5305 Rini et al. 2013 (INTORACT)]
-|2008-2010
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Temsirolimus_.26_Bevacizumab_999|Temsirolimus & Bevacizumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
-|-
-|}
-''<sup>1</sup>Reported efficacy for CALGB 90206 is based on the 2010 update and is based on a stratified analysis.''<br>
-''Note: Timing below reflects starting treatment on a Monday.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
-====Immunotherapy ====
-*[[Interferon alfa-2a (Roferon-A)]] 9,000,000 units SC once per day on days 1, 3, 5, 8, 10, 12 (3 times per week)
-'''14-day cycles'''
-</div>
-<div class="toccolours" style="background-color:#fff2ae">
-====Dose and schedule modifications====
-*[[Interferon alfa-2a (Roferon-A)]] dose can be reduced to 3,000,000 or 6,000,000 units SC 3 times per week based on tolerability
-</div></div>
-===References===
-#'''AVOREN:''' Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N; AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007 Dec 22;370(9605):2103-11. [https://doi.org/10.1016/S0140-6736(07)61904-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18156031/ PubMed] [https://clinicaltrials.gov/study/NCT00738530 NCT00738530]
-##'''Update:''' Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S, Sneller V. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol. 2010 May 1;28(13):2144-50. Epub 2010 Apr 5. [https://doi.org/10.1200/jco.2009.26.7849 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20368553/ PubMed]
-#'''CALGB 90206:''' Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008 Nov 20;26(33):5422-8. Epub 2008 Oct 20. [https://doi.org/10.1200/jco.2008.16.9847 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651074/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18936475/ PubMed] [https://clinicaltrials.gov/study/NCT00072046 NCT00072046]
-##'''Update:''' Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. 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 May 1;28(13):2137-43. Epub 2010 Apr 5. [https://doi.org/10.1200/jco.2009.26.5561 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860433/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20368558/ PubMed]
-#'''INTORACT:''' Rini BI, Bellmunt J, Clancy J, Wang K, Niethammer AG, Hariharan S, Escudier B. Randomized phase III trial of temsirolimus and bevacizumab versus interferon alfa and bevacizumab in metastatic renal cell carcinoma: INTORACT trial. J Clin Oncol. 2014 Mar 10;32(8):752-9. Epub 2013 Dec 2. [https://doi.org/10.1200/JCO.2013.50.5305 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24297945/ PubMed] [https://clinicaltrials.gov/study/NCT00631371 NCT00631371]
-==Erlotinib & Bevacizumab {{#subobject:1a1b7b|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:1e7b71|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.2007.11.5154 Bukowski et al. 2007]
-|2004
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
-|[[#Bevacizumab_monotherapy|Bevacizumab]]
-| style="background-color:#ffffbf" |Did not meet co-primary endpoints of ORR/PFS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-==== Targeted therapy====
-*[[Erlotinib (Tarceva)]] 150 mg PO once per day
-*[[Bevacizumab (Avastin)]] 10 mg/kg IV over 90 minutes once on day 1
-'''14-day cycle for up to 52 cycles (2 years)'''
-</div>
-<div class="toccolours" style="background-color:#fff2ae">
-====Dose and schedule modifications====
-*Bevacizumab infusion time can subsequently be reduced to 60 and 30 minute infusions as tolerated
-</div></div>
-===References===
-# Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, Drabkin HA, Dutcher J, Ryba S, Xia Q, Scappaticci FA, McDermott D. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. 2007 Oct 10;25(29):4536-41. Epub 2007 Sep 17. [https://doi.org/10.1200/jco.2007.11.5154 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17876014/ PubMed]
 ==Everolimus monotherapy {{#subobject:b3af63|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 294: / Line 150: @@
 <div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
-*RECORD-3, upon progression: [[#Sunitinib_monotherapy_3|Sunitinib]]
+*RECORD-3, upon progression: Second-line [[#Sunitinib_monotherapy_3|Sunitinib]]
 </div>
 <div class="toccolours" style="background-color:#fff2ae">
@@ Line 302: / Line 158: @@
 ===References===
 #'''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. [https://doi.org/10.1200/jco.2013.54.6911 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25049330/ PubMed] [https://clinicaltrials.gov/study/NCT00903175 NCT00903175]
-==Everolimus & Lenvatinib {{#subobject:e83gac|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:22bc4d|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-| rowspan="2" |[https://doi.org/10.1056/NEJMoa2035716 Motzer et al. 2021 (CLEAR)]
-| rowspan="2" |2016-10-13 to 2019-07-24
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|1. [[#Lenvatinib_.26_Pembrolizumab|Lenvatinib & Pembrolizumab]]
-| style="background-color:#d3d3d3" |Not reported
-|-
-|2. [[#Sunitinib_monotherapy_2|Sunitinib]]
-| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 14.7 vs 9.2 mo<br>(HR 0.65, 95% CI 0.53-0.80)
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Everolimus (Afinitor)]] 5 mg PO once per day on days 1 to 21
-*[[Lenvatinib (Lenvima)]] 18 mg PO once per day on days 1 to 21
-'''21-day cycles'''
-</div></div>
-===References===
-#'''CLEAR:''' Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, Kozlov V, Alyasova A, Hong SH, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK; CLEAR Trial Investigators. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021 Apr 8;384(14):1289-1300. Epub 2021 Feb 13. [https://doi.org/10.1056/NEJMoa2035716 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33616314/ PubMed] [https://clinicaltrials.gov/study/NCT02811861 NCT02811861]
-##'''Update:''' Choueiri TK, Eto M, Motzer R, De Giorgi U, Buchler T, Basappa NS, Méndez-Vidal MJ, Tjulandin S, Hoon Park S, Melichar B, Hutson T, Alemany C, McGregor B, Powles T, Grünwald V, Alekseev B, Rha SY, Kopyltsov E, Kapoor A, Alonso Gordoa T, Goh JC, Staehler M, Merchan JR, Xie R, Perini RF, Mody K, McKenzie J, Porta CG. Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study. Lancet Oncol. 2023 Mar;24(3):228-238. Erratum in: Lancet Oncol. 2023 Apr;24(4):e146. [https://doi.org/10.1016/s1470-2045(23)00049-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36858721/ PubMed]
 ==Gemcitabine & Sunitinib {{#subobject:ec76af|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:py1|Variant=1}}===
+===Regimen {{#subobject:py1|Variant=1}}===
 {| class="wikitable" style="width: 60%; text-align:center;"
 ! style="width: 33%" |Study
@@ Line 349: / Line 177: @@
 ====Targeted therapy====
 *[[Sunitinib (Sutent)]] 37.5 mg PO once per day on days 1 to 14
-'''21-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:e9a6b9|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 50%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1111/j.1464-410X.2011.10096.x Pandya et al. 2011]
-| style="background-color:#ffffbe" |Retrospective
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Gemcitabine (Gemzar)]] 750 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8
-====Targeted therapy====
-*[[Sunitinib (Sutent)]] 37.5 mg PO once per day on days 2 to 15
 '''21-day cycles'''
 </div></div>
 ===References===
-#'''Retrospective:''' Pandya SS, Mier JW, McDermott DF, Cho DC. Addition of gemcitabine at the time of sunitinib resistance in metastatic renal cell cancer. BJU Int. 2011 Oct;108(8 Pt 2):E245-9. Epub 2011 Feb 14. [https://doi.org/10.1111/j.1464-410X.2011.10096.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21320274/ PubMed]
 #'''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. [https://doi.org/10.1002/cncr.29503 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26058385/ PubMed] [https://clinicaltrials.gov/study/NCT00556049 NCT00556049]
 ==High-dose Interleukin-2 {{#subobject:d95f4e|Regimen=1}}==
@@ Line 384: / Line 194: @@
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://jamanetwork.com/journals/jama/article-abstract/368156 Rosenberg et al. 1994]
+|[https://doi.org/10.1001/jama.1994.03510360033032 Rosenberg et al. 1994]
 |1985-1992
 | style="background-color:#91cf61" |Non-randomized
@@ Line 444: / Line 254: @@
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 2.16 MU/kg/day, intermittent, goal 8.64 MU {{#subobject:9a662|Variant=1}}===
+===Regimen variant #3, 5 MU/m<sup>2</sup>/day, CI {{#subobject:bd04b6|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 50%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486432/ Klapper et al. 2008]
-| style="background-color:#ffffbe" |Retrospective
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
-*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours for up to 12 doses (reduced from originally up to 15 doses due to few patients tolerating 15 doses)
-** Then after 10 to 15 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours for up to 12 doses is given again
-====Supportive therapy====
-*"Routine administration of antipyretics, anti-inflammatories, antiemetics, antidiarrheals, and H2 antagonists."
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*After this one course of treatments--defined by the paper as "two cycles"--patients with stable to improved disease would receive additional courses of treatments every 2 months (no maximum number of courses listed)
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, 5 MU/m<sup>2</sup>/day, CI {{#subobject:bd04b6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
@@ Line 476: / Line 265: @@
 |1994-1997
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Interleukin-2_.26_TILs_777|IL-2 & CD8+ TILs]]
+|[[#Interleukin-2_.26_TILs_999|IL-2 & CD8+ TILs]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
@@ Line 486: / Line 275: @@
 </div></div>
 ===References===
-#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. [https://jamanetwork.com/journals/jama/article-abstract/368156 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8120958/ PubMed]
+#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. [https://doi.org/10.1001/jama.1994.03510360033032 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8120958/ PubMed]
 #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. [https://doi.org/10.1200/JCO.1994.12.8.1572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8040669/ PubMed]
 ##'''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. [https://doi.org/10.1200/jco.2003.02.122 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275327/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12915604/ PubMed]
@@ Line 492: / Line 281: @@
 #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. [https://doi.org/10.1200/JCO.1999.17.8.2521 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10561318/ PubMed]
 #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. [https://doi.org/10.1200/jco.2005.03.206 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15625368/ PubMed]
-#'''Retrospective:''' Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US, Sherry RM, Royal RE, Steinberg SM, Rosenberg S. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma : a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer. 2008 Jul 15;113(2):293-301. [https://doi.org/10.1002/cncr.23552 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486432/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18457330/ PubMed]
 ==Low-dose Interleukin-2 {{#subobject:a2e938|Regimen=1}}==
 LD IL-2: '''<u>L</u>'''ow-'''<u>D</u>'''ose '''<u>I</u>'''nter'''<u>L</u>'''eukin-'''<u>2</u>'''
@@ Line 571: / Line 359: @@
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
-*[[Interferon alfa-2a (Roferon-A)]] 5,000,000 units SC 5 times per week
+*[[Interferon alfa-2a (Roferon-A)]] 5,000,000 units SC once per day on days 1 to 5 (5 times per week)
-'''Continued indefinitely'''
+'''7-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 9 MU TIW {{#subobject:524ccc|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 589: / Line 378: @@
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651074/ Rini et al. 2008 (CALGB 90206)]
+|[https://doi.org/10.1158/1078-0432.ccr-15-0580 Hawkins et al. 2016 (Active Biotech 06762004)]
-|2003-2005
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Bevacizumab_.26_Interferon_alfa-2a|Bevacizumab & Interferon alfa-2a]]
-| style="background-color:#fee08b" |Might have inferior OS<sup>1</sup>
-|-
-|[https://doi.org/10.1016/S0140-6736(07)61904-7 Escudier et al. 2007 (AVOREN)]
-|2004-06 to 2005-10
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Bevacizumab_.26_Interferon_alfa-2a|Bevacizumab & Interferon alfa-2a]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>2</sup>
-|-
-|[https://doi.org/10.1200/jco.2008.19.3342 Escudier et al. 2009 (Bayer 11848)]
-|2005-06-28 to 2005-09-30
-| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[[#Sorafenib_monotherapy|Sorafenib]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
-|-
-|[http://clincancerres.aacrjournals.org/content/22/13/3172.long Hawkins et al. 2016 (Active Biotech 06762004)]
 |2007-2010
 | style="background-color:#1a9851" |Phase 2/3 (C)
-|[[#Naptumomab estafenatox_.26_Interferon_alfa_777|Naptumomab estafenatox + IFNα]]
+|[[#Naptumomab estafenatox_.26_Interferon_alfa_999|Naptumomab estafenatox + IFNα]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''<sup>1</sup>Reported efficacy for CALGB 90206 is based on the 2010 update and is based on a stratified analysis.''<br>
-''<sup>2</sup>Reported efficacy for AVOREN is based on the 2010 update.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
@@ Line 626: / Line 395: @@
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 9 MU daily, with lead-in {{#subobject:5f04fc|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 637: / Line 407: @@
 |1994-1996
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Interferon_alfa_.26_13-CRA_777|IFN alfa & 13-CRA]]
+|[[#Interferon_alfa_.26_13-CRA_999|IFN alfa & 13-CRA]]
 | style="background-color:#ffffbf" | Did not meet primary endpoint of ORR
 |-
 |}
+''Note: Interferon alfa-2a dose was increased only if the prior dose was tolerated.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Interferon alfa-2a (Roferon-A)]] as follows:
-**Week 1: 3,000,000 units SC once per day
+**Cycle 1: 3,000,000 units SC once per day on days 1 to 7
-**Week 2 (if prior dose tolerated): 6,000,000 units SC once per day
+**Cycle 2: 6,000,000 units SC once per day on days 1 to 7
-**Week 3 onwards (if prior dose tolerated): 9,000,000 units SC once per day
+**Cycle 3 onwards: 9,000,000 units SC once per day on days 1 to 7
-'''Continued indefinitely'''
+'''7-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, 9 MU TIW, with lead-in {{#subobject:2c65a4|Variant=1}}===
+===Regimen variant #4, 10 MU TIW, with lead-in {{#subobject:leadd5|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
@@ Line 658: / Line 429: @@
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/NEJMoa065044 Motzer et al. 2007 (A618-1034)]
+|[https://doi.org/10.1016/S0140-6736(98)03544-2 Ritchie et al. 1999 (MRC RE01)]
-|2004-08 to 2005-10
+|1992-1997
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
-|[[#Sunitinib_monotherapy_2|Sunitinib]]
+|[[Renal_cell_carcinoma_-_historical#Medroxyprogesterone_acetate_monotherapy|MPA]]
-| style="background-color:#d73027" |Inferior PFS
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 8.5 vs 6 mo<br>(HR 0.72, 95% CI 0.55-0.94)
 |-
 |}
@@ Line 668: / Line 439: @@
 ====Immunotherapy====
 *[[Interferon alfa-2a (Roferon-A)]] as follows:
-**Week 1: 3,000,000 units SC 3 times per week
+**Cycle 1: 5,000,000 units SC once per day on days 1 & 3, then 10,000,000 units SC once on day 5
-**Week 2 (if prior dose tolerated): 6,000,000 units SC 3 times per week
+**Cycles 2 to 12: 10,000,000 units SC once per day on days 1, 3, 5 (3 times per week)
-**Week 3 onwards (if prior dose tolerated): 9,000,000 units SC 3 times per week
+'''7-day cycle for 12 cycles'''
-'''Continued indefinitely'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 681: / Line 451: @@
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1016/S0140-6736(98)03544-2 Ritchie et al. 1999 (MRC RE01)]
-|1992-1997
-| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
-|[[Renal_cell_carcinoma_-_historical#Medroxyprogesterone_acetate_monotherapy|MPA]]
-| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 8.5 vs 6 mo<br>(HR 0.72, 95% CI 0.55-0.94)
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835851/ Gore et al. 2010 (MRC RE04/EORTC GU 30012)]
@@ Line 697: / Line 461: @@
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
-*[[Interferon alfa-2a (Roferon-A)]] 10,000,000 units SC 3 times per week
+*[[Interferon alfa-2a (Roferon-A)]] 10,000,000 units SC once per day on days 1, 3, 5 (3 times per week)
-**In MRC RE01, the first two doses were 5,000,000 units
+'''7-day cycles'''
-'''12-week course (MRC RE01) or continued indefinitely (MRC RE04/EORTC GU 30012)'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 727: / Line 490: @@
 |-
 |}
+''Note: Interferon alfa-2a dose was increased only if the prior dose was tolerated.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Interferon alfa-2a (Roferon-A)]] as follows:
-**Week 1: 3,000,000 units SC 3 times per week
+**Cycle 1: 3,000,000 units SC once per day on days 1, 3, 5
-**Week 2 (if prior dose tolerated): 9,000,000 units SC 3 times per week
+**Cycle 2: 9,000,000 units SC once per day on days 1, 3, 5
-**Week 3 onwards (if prior dose tolerated): 18,000,000 units SC 3 times per week
+**Cycle 3 onwards: 18,000,000 units SC once per day on days 1, 3, 5
-***If higher doses cannot be tolerated, highest tolerable doses of 3,000,000, 4,500,500, or 6,000,000 units can be used
+'''7-day cycles'''
-'''Continued indefinitely'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====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
 </div></div>
 === References===
@@ Line 741: / Line 508: @@
 #'''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. [https://doi.org/10.1016/S0140-6736(98)03544-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10023944/ PubMed]
 #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. [https://doi.org/10.1200/JCO.2000.18.16.2972 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10944130/ PubMed]
-#'''A618-1034:''' Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. [https://doi.org/10.1056/NEJMoa065044 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17215529/ PubMed] [https://clinicaltrials.gov/study/NCT00098657 NCT00098657]
-##'''Update:''' Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Aug 1;27(22):3584-90. Epub 2009 Jun 1. [https://doi.org/10.1200/jco.2008.20.1293 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646307/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19487381/ PubMed] content property of [https://hemonc.org HemOnc.org]
 #'''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. [https://doi.org/10.1056/NEJMoa066838 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17538086/ PubMed] [https://clinicaltrials.gov/study/NCT00065468 NCT00065468]
-#'''AVOREN:''' Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N; AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007 Dec 22;370(9605):2103-11. [https://doi.org/10.1016/S0140-6736(07)61904-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18156031/ PubMed] [https://clinicaltrials.gov/study/NCT00738530 NCT00738530]
-##'''Update:''' Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S, Sneller V. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol. 2010 May 1;28(13):2144-50. Epub 2010 Apr 5. [https://doi.org/10.1200/jco.2009.26.7849 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20368553/ PubMed]
-#'''CALGB 90206:''' Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008 Nov 20;26(33):5422-8. Epub 2008 Oct 20. [https://doi.org/10.1200/jco.2008.16.9847 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651074/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18936475/ PubMed] [https://clinicaltrials.gov/study/NCT00072046 NCT00072046]
-##'''Update:''' Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. 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 May 1;28(13):2137-43. Epub 2010 Apr 5. [https://doi.org/10.1200/jco.2009.26.5561 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860433/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20368558/ PubMed]
-#'''Bayer 11848:''' Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F, Negrier S, Laferriere N, Scheuring UJ, Cella D, Shah S, Bukowski RM. 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 Mar 10;27(8):1280-9. Epub 2009 Jan 26. Erratum in: J Clin Oncol. 2009 May 1; 27(13):2305. [https://doi.org/10.1200/jco.2008.19.3342 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19171708/ PubMed] [https://clinicaltrials.gov/study/NCT00117637 NCT00117637]
 #'''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. [https://doi.org/10.1016/S0140-6736(09)61921-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835851/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20153039/ PubMed] [https://clinicaltrials.gov/study/NCT00053820 NCT00053820]
-#'''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. [http://clincancerres.aacrjournals.org/content/22/13/3172.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26851187/ PubMed] [https://clinicaltrials.gov/study/NCT00420888 NCT00420888]
+#'''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. [https://doi.org/10.1158/1078-0432.ccr-15-0580 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26851187/ PubMed] [https://clinicaltrials.gov/study/NCT00420888 NCT00420888]
-==Lenvatinib & Pembrolizumab {{#subobject:e83gac|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-=== Regimen variant #1 {{#subobject:22bc4d|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-| rowspan="2" |[https://doi.org/10.1056/NEJMoa2035716 Motzer et al. 2021 (CLEAR)]
-<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-284-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-|-
-|} -->
-| rowspan="2" |2016-10-13 to 2019-07-24
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-| 1. [[#Everolimus_.26_Lenvatinib|Everolimus & Lenvatinib]]
-| style="background-color:#d3d3d3" |Not reported
-|-
-|2. [[#Sunitinib_monotherapy_2|Sunitinib]]
-| style="background-color:#1a9850" |Superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: NYR vs NYR<br>(HR 0.72, 95% CI 0.55-0.93)
-|-
-|}
-''<sup>1</sup>Reported efficacy is based on the 2023 update.''
-<div class="toccolours" style="background-color:#b3e2cd">
-==== Targeted therapy====
-*[[Lenvatinib (Lenvima)]] 20 mg PO once per day on days 1 to 21
-====Immunotherapy====
-*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
-'''21-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:22bug8|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.clinicaltrials.gov/study/NCT04736706 Awaiting publication (MK-6482-012)]
-|2021-ongoing
-| style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Belzutifan.2C_Lenvatinib.2C_Pembrolizumab_666|Belzutifan, Lenvatinib, Pembrolizumab]]<br>2. [[#Lenvatinib.2C_Pembrolizumab.2C_Quavonlimab_777|Lenvatinib, Pembrolizumab, Quavonlimab]]
-| style="background-color:#d3d3d3" |TBD if different co-primary endpoints of PFS/OS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Lenvatinib (Lenvima)]] 20 mg PO once per day on days 1 to 42
-====Immunotherapy====
-*[[Pembrolizumab (Keytruda)]] as follows:
-**Cycles 1 to 18: 400 mg IV once on day 1
-'''42-day cycles'''
-</div></div>
-===References===
-#'''CLEAR:''' Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, Kozlov V, Alyasova A, Hong SH, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK; CLEAR Trial Investigators. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021 Apr 8;384(14):1289-1300. Epub 2021 Feb 13. [https://doi.org/10.1056/NEJMoa2035716 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33616314/ PubMed] [https://clinicaltrials.gov/study/NCT02811861 NCT02811861]
-##'''Update:''' Choueiri TK, Eto M, Motzer R, De Giorgi U, Buchler T, Basappa NS, Méndez-Vidal MJ, Tjulandin S, Hoon Park S, Melichar B, Hutson T, Alemany C, McGregor B, Powles T, Grünwald V, Alekseev B, Rha SY, Kopyltsov E, Kapoor A, Alonso Gordoa T, Goh JC, Staehler M, Merchan JR, Xie R, Perini RF, Mody K, McKenzie J, Porta CG. Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study. Lancet Oncol. 2023 Mar;24(3):228-238. Erratum in: Lancet Oncol. 2023 Apr;24(4):e146. [https://doi.org/10.1016/s1470-2045(23)00049-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36858721/ PubMed]
-#'''MK-6482-012:''' [https://clinicaltrials.gov/study/NCT04736706 NCT04736706]
-==Regorafenib monotherapy {{#subobject:183793|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:a55057|Variant=1}}===
-{| class="wikitable sortable" style="width: 80%; text-align:center;"
-! style="width: 25%" | Study
-! style="width: 25%" |Dates of enrollment
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1016/S1470-2045(12)70364-9 Eisen et al. 2012 (Bayer 11726)]
-|2008-2011
-| style="background-color:#91cf61" |Phase 2
-|ORR: 40% (90% CI 28-53%)
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21, given while fasting or after a light meal
-'''28-day cycles'''
-</div></div>
-=== References===
-#'''Bayer 11726:''' Eisen T, Joensuu H, Nathan PD, Harper PG, Wojtukiewicz MZ, Nicholson S, Bahl A, Tomczak P, Pyrhonen S, Fife K, Bono P, Boxall J, Wagner A, Jeffers M, Lin T, Quinn DI. Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: a single-group phase 2 trial. Lancet Oncol. 2012 Oct;13(10):1055-62. Epub 2012 Sep 6. [https://doi.org/10.1016/S1470-2045(12)70364-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22959186/ PubMed] [https://clinicaltrials.gov/study/NCT00664326 NCT00664326]
 ==Sorafenib monotherapy {{#subobject:fe45b0|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 844: / Line 521: @@
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.2008.19.3342 Escudier et al. 2009 (Bayer 11848)]
-|2005-06-28 to 2005-09-30
-| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ooc)
-|[[#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
 |[https://doi.org/10.1002/cncr.24864 Stadler et al. 2010 (ARCCS)]
@@ Line 856: / Line 527: @@
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
-|-
-|[https://doi.org/10.1016/j.clgc.2020.01.001 Tomita et al. 2020 (CROSS-J-RCC)]
-|2010-2012
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Sunitinib_monotherapy_2|Sunitinib]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
 |[https://doi.org/10.1016/j.ejca.2018.11.001 Retz et al. 2018 (SWITCH-II)]
@@ Line 884: / Line 549: @@
 </div></div>
 ===References===
-#'''Bayer 11848:''' Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F, Negrier S, Laferriere N, Scheuring UJ, Cella D, Shah S, Bukowski RM. 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 Mar 10;27(8):1280-9. Epub 2009 Jan 26. Erratum in: J Clin Oncol. 2009 May 1; 27(13):2305. [https://doi.org/10.1200/jco.2008.19.3342 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19171708/ PubMed] [https://clinicaltrials.gov/study/NCT00117637 NCT00117637]
 #'''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. [https://doi.org/10.1002/cncr.24864 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20082451/ PubMed] [https://clinicaltrials.gov/study/NCT00111020 NCT00111020]
 #'''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. [https://doi.org/10.1016/j.ejca.2018.11.001 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30529901/ PubMed] [https://clinicaltrials.gov/study/NCT01613846 NCT01613846]
-#'''CROSS-J-RCC:''' Tomita Y, Naito S, Sassa N, Takahashi A, Kondo T, Koie T, Obara W, Kobayashi Y, Teishima J, Takahashi M, Matsuyama H, Ueda T, Yamaguchi K, Kishida T, Shiroki R, Saika T, Shinohara N, Oya M, Kanayama HO. Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC. Clin Genitourin Cancer. 2020 Aug;18(4):e374-e385. Epub 2020 Mar 6. [https://doi.org/10.1016/j.clgc.2020.01.001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32466961/ PubMed] [https://clinicaltrials.gov/study/NCT01481870 NCT01481870]
 ==Sunitinib monotherapy {{#subobject:b4a97a|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 4 out of 6 weeks {{#subobject:92e618|Variant=1}}===
+===Regimen {{#subobject:92e618|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
@@ Line 898: / Line 561: @@
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1056/NEJMoa065044 Motzer et al. 2007 (A618-1034)]
-<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-106-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-|-
-|} -->
-|2004-08 to 2005-10
-| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
-|[[#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]]
-| style="background-color:#d9ef8b" |Superior PFS (primary endpoint)<br>Median PFS: 11 vs 5 mo<br>(HR 0.42, 95% CI 0.32-0.54)<br><br>Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 26.4 vs 21.8 mo<br>(HR 0.82, 95% CI 0.67-1.001)
 |-
 |[https://doi.org/10.1016/S1470-2045%2809%2970162-7 Gore et al. 2009 (A618-1037)]
@@ Line 914: / Line 567: @@
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
-|-
-|[https://doi.org/10.1158/1078-0432.CCR-10-2082 Amato et al. 2010 (TroVax Renal Immunotherapy Survival Trial)]
-|2006-2008
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#MVA-5T4_.26_Sunitinib_777|Sunitinib & MVA-5T4]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 19.2 vs 20.1 mo<br>(HR 0.93, 95% CI 0.76-1.16)
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ Motzer et al. 2014 (RECORD-3)]
@@ Line 932: / Line 579: @@
 |[[#Sorafenib_monotherapy|Sorafenib]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
-|-
-|[https://doi.org/10.1056/NEJMoa1803675 Méjean et al. 2018 (CARMENA)]
-|2009-2017
-| style="background-color:#1a9851" | Phase 3 (E-de-esc)
-|Nephrectomy, then [[#Sunitinib_monotherapy_2|Sunitinib]]
-| style="background-color:#eeee01" |Non-inferior OS (primary endpoint)<br>Median OS: 18.4 vs 13.9 mo<br>(HR 0.89, 95% CI 0.71-1.10)
-|-
-|[https://doi.org/10.1016/S1470-2045(16)30408-9 Rini et al. 2016 (IMPRINT)]
-|2010-2012
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#IMA-901_.26_Sunitinib_777|Sunitinib & IMA-901]]
-| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: NYR vs 33.2 mo<br>(HR 0.75, 95% CI 0.54-1.04)
-|-
-|[https://doi.org/10.1016/j.clgc.2020.01.001 Tomita et al. 2020 (CROSS-J-RCC)]
-|2010-2012
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Sorafenib_monotherapy|Sorafenib]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
-|-
-|[https://doi.org/10.1158/1078-0432.ccr-19-2427 Figlin et al. 2020 (ADAPT)]
-|2013-2016
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Rocapuldencel-T_.26_Sunitinib_777|Rocapuldencel-T & Sunitinib]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 32.4 vs 27.7 mo<br>(HR 0.91, 95% CI 0.71-1.20)
 |-
 |[https://doi.org/10.1016/S0140-6736(19)30723-8 Rini et al. 2019 (IMmotion151)]
@@ Line 962: / Line 585: @@
 |[[#Atezolizumab_.26_Bevacizumab|Atezolizumab & Bevacizumab]]
 | style="background-color:#fc8d59" |Seems to have inferior PFS
-|-
-| rowspan="2" |[https://doi.org/10.1056/NEJMoa2035716 Motzer et al. 2021 (CLEAR)]
-| rowspan="2" |2016-10-13 to 2019-07-24
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Everolimus_.26_Lenvatinib|Everolimus & Lenvatinib]]
-| style="background-color:#d73027" |Inferior PFS
-|-
-|2. [[#Lenvatinib_.26_Pembrolizumab|Lenvatinib & Pembrolizumab]]
-| style="background-color:#d73027" |Inferior OS
-|-
-|[https://www.clinicaltrials.gov/study/NCT04394975 Awaiting publication (JS001-036-III-RCC)]
-|2020-ongoing
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Axitinb_.26_Toripalimab_666|Axitinib & Toripalimab]]
-| style="background-color:#d3d3d3" |TBD if different primary endpoint of PFS
 |-
 |}
-''<sup>1</sup>Reported efficacy for A618-1034 is based on the 2009 update.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
@@ Line 986: / Line 593: @@
 </div>
 <div class="toccolours" style="background-color:#cbd5e7">
-==== Subsequent treatment====
+====Subsequent treatment====
-*SWITCH, upon progression: [[#Sorafenib_monotherapy_2|Sorafenib]]
+*SWITCH, upon progression: Second-line [[#Sorafenib_monotherapy_2|Sorafenib]]
 </div>
 <div class="toccolours" style="background-color:#fff2ae">
 ====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
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 2 out of 4 weeks {{#subobject:92ejg8|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.clinicaltrials.gov/study/NCT04523272 Awaiting publication (TQB2450-III-07)]
-| 2020-ongoing
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Anlotinib_.26_TQB-2450_777|Anlotinib & TQB-2450]]
-| style="background-color:#d3d3d3" |TBD if different primary endpoint of PFS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Sunitinib (Sutent)]] 50 mg PO once per day on days 1 to 14
-'''28-day cycles'''
 </div></div>
 ===References===
-#'''A618-1034:''' Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. [https://doi.org/10.1056/NEJMoa065044 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17215529/ PubMed] [https://clinicaltrials.gov/study/NCT00098657 NCT00098657]
-##'''Update:''' Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Aug 1;27(22):3584-90. Epub 2009 Jun 1. [https://doi.org/10.1200/jco.2008.20.1293 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646307/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19487381/ PubMed]
 #'''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. [https://doi.org/10.1016/S1470-2045%2809%2970162-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19615940/ PubMed] [https://clinicaltrials.gov/study/NCT00130897 NCT00130897]
-#'''TroVax Renal Immunotherapy Survival Trial:''' Amato RJ, Hawkins RE, Kaufman HL, Thompson JA, Tomczak P, Szczylik C, McDonald M, Eastty S, Shingler WH, de Belin J, Goonewardena M, Naylor S, Harrop R. Vaccination of metastatic renal cancer patients with MVA-5T4: a randomized, double-blind, placebo-controlled phase III study. Clin Cancer Res. 2010 Nov 15;16(22):5539-47. Epub 2010 Sep 29. [https://doi.org/10.1158/1078-0432.CCR-10-2082 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20881001/ PubMed] [https://clinicaltrials.gov/study/NCT00397345 NCT00397345]
 #'''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. [https://doi.org/10.1200/JCO.2013.50.8267 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24687826/ PubMed] [https://clinicaltrials.gov/study/NCT01064310 NCT01064310]
 #'''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. [https://doi.org/10.1200/jco.2013.54.6911 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25049330/ PubMed] [https://clinicaltrials.gov/study/NCT00903175 NCT00903175]
 #'''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. [https://doi.org/10.1016/j.eururo.2015.04.017 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25952317/ PubMed] [https://clinicaltrials.gov/study/NCT00732914 NCT00732914]
-#'''IMPRINT:''' Rini BI, Stenzl A, Zdrojowy R, Kogan M, Shkolnik M, Oudard S, Weikert S, Bracarda S, Crabb SJ, Bedke J, Ludwig J, Maurer D, Mendrzyk R, Wagner C, Mahr A, Fritsche J, Weinschenk T, Walter S, Kirner A, Singh-Jasuja H, Reinhardt C, Eisen T. IMA901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as first-line therapy for advanced or metastatic renal cell carcinoma (IMPRINT): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2016 Nov;17(11):1599-1611. [https://doi.org/10.1016/S1470-2045(16)30408-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27720136/ PubMed] [https://clinicaltrials.gov/study/NCT01265901 NCT01265901]
-#'''CARMENA:''' Méjean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, Geoffrois L, Thiery-Vuillemin A, Cormier L, Lang H, Guy L, Gravis G, Rolland F, Linassier C, Lechevallier E, Beisland C, Aitchison M, Oudard S, Patard JJ, Theodore C, Chevreau C, Laguerre B, Hubert J, Gross-Goupil M, Bernhard JC, Albiges L, Timsit MO, Lebret T, Escudier B. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med. 2018 Aug 2;379(5):417-427. Epub 2018 Jun 3. [https://doi.org/10.1056/NEJMoa1803675 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29860937/ PubMed] [https://clinicaltrials.gov/study/NCT00930033 NCT00930033]
 #'''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. [https://doi.org/10.1016/S0140-6736(19)30723-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31079938/ PubMed] [https://clinicaltrials.gov/study/NCT02420821 NCT02420821]
 ##'''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. [https://doi.org/10.1001/jamaoncol.2021.5981 link to original article] [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855230/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34940781/ PubMed]
-#'''ADAPT:''' Figlin RA, Tannir NM, Uzzo RG, Tykodi SS, Chen DYT, Master V, Kapoor A, Vaena D, Lowrance W, Bratslavsky G, DeBenedette M, Gamble A, Plachco A, Norris MS, Horvatinovich J, Tcherepanova IY, Nicolette CA, Wood CG; ADAPT study group. Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma. Clin Cancer Res. 2020 May 15;26(10):2327-2336. Epub 2020 Feb 7. [https://doi.org/10.1158/1078-0432.ccr-19-2427 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32034074/ PubMed] [https://clinicaltrials.gov/study/NCT01582672 NCT01582672]
-#'''CROSS-J-RCC:''' Tomita Y, Naito S, Sassa N, Takahashi A, Kondo T, Koie T, Obara W, Kobayashi Y, Teishima J, Takahashi M, Matsuyama H, Ueda T, Yamaguchi K, Kishida T, Shiroki R, Saika T, Shinohara N, Oya M, Kanayama HO. Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC. Clin Genitourin Cancer. 2020 Aug;18(4):e374-e385. Epub 2020 Mar 6. [https://doi.org/10.1016/j.clgc.2020.01.001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32466961/ PubMed] [https://clinicaltrials.gov/study/NCT01481870 NCT01481870]
-#'''CLEAR:''' Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, Kozlov V, Alyasova A, Hong SH, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK; CLEAR Trial Investigators. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021 Apr 8;384(14):1289-1300. Epub 2021 Feb 13. [https://doi.org/10.1056/NEJMoa2035716 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33616314/ PubMed] [https://clinicaltrials.gov/study/NCT02811861 NCT02811861]
-##'''Update:''' Choueiri TK, Eto M, Motzer R, De Giorgi U, Buchler T, Basappa NS, Méndez-Vidal MJ, Tjulandin S, Hoon Park S, Melichar B, Hutson T, Alemany C, McGregor B, Powles T, Grünwald V, Alekseev B, Rha SY, Kopyltsov E, Kapoor A, Alonso Gordoa T, Goh JC, Staehler M, Merchan JR, Xie R, Perini RF, Mody K, McKenzie J, Porta CG. Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study. Lancet Oncol. 2023 Mar;24(3):228-238. Erratum in: Lancet Oncol. 2023 Apr;24(4):e146. [https://doi.org/10.1016/s1470-2045(23)00049-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36858721/ PubMed]
-#'''KEYNOTE-679:''' [https://clinicaltrials.gov/study/NCT03260894 NCT03260894]
-#'''JS001-036-III-RCC:''' [https://clinicaltrials.gov/study/NCT04394975 NCT04394975]
-#'''PIVOT-09:''' [https://clinicaltrials.gov/study/NCT03729245 NCT03729245]
-#'''TQB2450-III-07:''' [https://clinicaltrials.gov/study/NCT04523272 NCT04523272]
 ==Temsirolimus monotherapy {{#subobject:8160ec|Regimen=1}}==
@@ Line 1,067: / Line 640: @@
 =Metastatic disease, second-line=
-==Bevacizumab monotherapy {{#subobject:dc7874|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-=== Regimen {{#subobject:24489f|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275324/ Yang et al. 2003]
-|1998-2001
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
-|[[Renal_cell_carcinoma_-_null_regimens#Placebo_3|Placebo]]
-| style="background-color:#1a9850" |Superior TTP (primary endpoint)
-|-
-|}
-<div class="toccolours" style="background-color:#fdcdac">
-====Prior treatment criteria====
-*Previous therapy with IL-2 or contraindication to IL-2
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
-'''14-day cycles'''
-</div></div>
-===References===
-#Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003 Jul 31;349(5):427-34. [https://doi.org/10.1056/NEJMoa021491 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275324/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/12890841/ PubMed]
 ==Cabozantinib monotherapy {{#subobject:pyr1|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 1,108: / Line 653: @@
 ! style="width: 20%" | Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024539/ Choueiri et al. 2015 (METEOR)]
-<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-111-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
-|-
-|} -->
-|2013-08 to 2014-11
-| style="background-color:#1a9851" | Phase 3 (E-RT-switch-ic)
-|[[#Everolimus_monotherapy_2|Everolimus]]
-| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 7.4 vs 3.8 mo<br>(HR 0.58, 95% CI 0.45-0.75)<br><br>Superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 21.4 vs 17.1 mo<br>(HR 0.70, 95% CI 0.58-0.85)
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437824/ Tannir et al. 2022 (CANTATA)]
-|2018-11-27 to 2019-09-30
-| style="background-color:#1a9851" | Phase 3 (C)
-|[[#Cabozantinib_.26_Telaglenastat_777|Cabozantinib & Telaglenastat]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
 |[https://doi.org/10.1016/s0140-6736(23)00922-4 Pal et al. 2023 (CONTACT-03)]
@@ Line 1,132: / Line 661: @@
 |-
 |}
-''<sup>1</sup>Reported efficacy is based on the 2018 update.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Prior treatment criteria====
-*METEOR: [[Regimen_classes#VEGFR_inhibitor_therapy|VEGFR TKI]], with progression
-*CANTATA: 1 to 2 prior lines of therapy, including 1 or more antiangiogenic therapies or Ipilimumab & Nivolumab
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Cabozantinib (Cometriq)|Cabozantinib (Cabometyx)]] 60 mg PO once per day on days 1 to 28
+*[[Cabozantinib (Cometriq)|Cabozantinib (Cabometyx)]] 60 mg PO once per day on days 1 to 28, taken at least 2 hours before or 1 hour after meals
-**At least 2 hours before or 1 hour after meals according to the [https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf Cabozantinib (Cabometyx) package insert]
 '''28-day cycles'''
 </div></div>
 ===References===
-#'''METEOR:''' Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Géczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ; METEOR Investigators. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. Epub 2015 Sep 25. [https://doi.org/10.1056/NEJMoa1510016 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024539/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26406150/ PubMed] [https://clinicaltrials.gov/study/NCT01865747 NCT01865747]
-##'''Update:''' Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DY, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ; METEOR investigators. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-27. Epub 2016 Jun 5. [https://doi.org/10.1016/S1470-2045(16)30107-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27279544/ PubMed]
-##'''HRQoL analysis:''' Cella D, Escudier B, Tannir NM, Powles T, Donskov F, Peltola K, Schmidinger M, Heng DYC, Mainwaring PN, Hammers HJ, Lee JL, Roth BJ, Marteau F, Williams P, Baer J, Mangeshkar M, Scheffold C, Hutson TE, Pal S, Motzer RJ, Choueiri TK. Quality of life outcomes for cabozantinib versus everolimus in patients with metastatic renal cell carcinoma: METEOR phase III randomized trial. J Clin Oncol. 2018 Mar 10;36(8):757-764. Epub 2018 Jan 29. [https://doi.org/10.1200/JCO.2017.75.2170 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6804841/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29377755/ PubMed]
-##'''Update:''' Motzer RJ, Escudier B, Powles T, Scheffold C, Choueiri TK. Long-term follow-up of overall survival for cabozantinib versus everolimus in advanced renal cell carcinoma. Br J Cancer. 2018 May;118(9):1176-1178. Epub 2018 Mar 26. [https://doi.org/10.1038/s41416-018-0061-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943250/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29576624/ PubMed]
-#'''CANTATA:''' Tannir NM, Agarwal N, Porta C, Lawrence NJ, Motzer R, McGregor B, Lee RJ, Jain RK, Davis N, Appleman LJ, Goodman O Jr, Stadler WM, Gandhi S, Geynisman DM, Iacovelli R, Mellado B, Sepúlveda Sánchez JM, Figlin R, Powles T, Akella L, Orford K, Escudier B. Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial. JAMA Oncol. 2022 Oct 1;8(10):1411-1418. [https://doi.org/10.1001/jamaoncol.2022.3511 link to orginal article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437824/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36048457/ PubMed] [https://clinicaltrials.gov/study/NCT03428217 NCT03428217]
 #'''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. [https://doi.org/10.1016/s0140-6736(23)00922-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/37290461/ PubMed] [https://clinicaltrials.gov/study/NCT04338269 NCT04338269]
-#'''MK-6482-011:''' [https://clinicaltrials.gov/study/NCT04586231 NCT04586231]
 ==Everolimus monotherapy {{#subobject:893557|Regimen=1}}==
@@ Line 1,163: / Line 678: @@
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1016/S0140-6736(08)61039-9 Motzer et al. 2008 (RECORD-1)]
-<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-108-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
-|-
-|} -->
-|2006-04 to 2007-04
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[Renal_cell_carcinoma_-_null_regimens#Placebo_2|Placebo]]
-| style="background-color:#1a9850" |Superior PFS<sup>1</sup> (primary endpoint)<br>Median PFS: 4.9 vs 1.9 mo<br>(HR 0.33, 95% CI 0.25-0.43)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 14.8 vs 14.4 mo<br>(HR 0.87, 95% CI 0.65-1.15)
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ Motzer et al. 2014 (RECORD-3)]
@@ Line 1,179: / Line 684: @@
 |[[#Sunitinib_monotherapy_3|Sunitinib]]
 | style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS (primary endpoint)
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006123/ Motzer et al. 2015 (RECORD-4)]
-|2011-2013
-| style="background-color:#91cf61" |Phase 2
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5719487/ Motzer et al. 2015 (CheckMate 025)]
-|2012-2014
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Nivolumab_monotherapy|Nivolumab]]
-| style="background-color:#d73027" |Inferior OS
-|-
-| rowspan="2" |[https://doi.org/10.1016/S1470-2045(15)00290-9 Motzer et al. 2015 (E7080-G000-205)]
-| rowspan="2" |2012-03-16 to 2013-06-19
-| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (C)
-|1. [[#Everolimus_.26_Lenvatinib | Everolimus & Lenvatinib]]
-| style="background-color:#d73027" |Inferior PFS
-|-
-|2. [[#Lenvatinib_monotherapy|Lenvatinib]]
-| style="background-color:#fc8d59" |Seems to have inferior PFS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024539/ Choueiri et al. 2015 (METEOR)]
-|2013-08 to 2014-11
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cabozantinib_monotherapy_2|Cabozantinib]]
-| style="background-color:#d73027" |Inferior OS
-|-
-| rowspan="2" |[https://doi.org/10.1016/j.ejca.2022.10.025 Sheng et al. 2022 (CONCEPT<sub>RCC</sub>)]
-| rowspan="2" | 2017-2019
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-| 1. [[#Everolimus_.26_Vorolanib_777|Everolimus & Vorolanib]]
-| style="background-color:#d73027" |Inferior PFS
-|-
-|2. [[#Vorolanib_monotherapy_777|Vorolanib]]
-| style="background-color:#fee08b" |Might have inferior PFS
 |-
 |}
-''<sup>1</sup>Reported efficacy for RECORD-1 is based on the 2010 update.''<br>
-''Note: 72% of patients in Checkmate 025 had anti-angiogenic therapy prior to progression.''
 <div class="toccolours" style="background-color:#fdcdac">
 ====Prior treatment criteria====
-*RECORD-1 & METEOR: [[Regimen_classes#VEGFR_inhibitor_therapy|VEGFR TKI]], with progression
 *RECORD-3: [[#Sunitinib_monotherapy_2|Sunitinib]], with progression
-*CONCEPT<sub>RCC</sub>: One prior [[Regimen_classes#VEGFR_inhibitor_therapy|VEGFR TKI]]
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
@@ Line 1,235: / Line 700: @@
 </div></div>
 ===References===
-#'''RECORD-1:''' Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. Epub 2008 Jul 22. [https://doi.org/10.1016/S0140-6736(08)61039-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18653228/ PubMed] [https://clinicaltrials.gov/study/NCT00410124 NCT00410124]
-##'''Update:''' Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer. 2010 Sep 15;116(18):4256-65. [https://doi.org/10.1002/cncr.25219 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20549832/ PubMed]
 #'''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. [https://doi.org/10.1200/jco.2013.54.6911 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25049330/ PubMed] [https://clinicaltrials.gov/study/NCT00903175 NCT00903175]
-#'''CheckMate 025:''' Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015 Nov 5;373(19):1803-13. Epub 2015 Sep 25. [https://doi.org/10.1056/NEJMoa1510665 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5719487/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26406148/ PubMed] [https://clinicaltrials.gov/study/NCT01668784 NCT01668784]
-##'''HRQoL analysis:''' Cella D, Grünwald V, Nathan P, Doan J, Dastani H, Taylor F, Bennett B, DeRosa M, Berry S, Broglio K, Berghorn E, Motzer RJ. Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimus in CheckMate 025: a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):994-1003. Epub 2016 Jun 6. Erratum in: Lancet Oncol. 2016 Jul;17 (7):e270. [https://doi.org/10.1016/S1470-2045(16)30125-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27283863/ PubMed]
-##'''Subgroup analysis:''' Escudier B, Sharma P, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Gurney H, Donskov F, Peltola K, Wagstaff J, Gauler TC, Ueda T, Zhao H, Waxman IM, Motzer RJ; CheckMate 025 investigators. CheckMate 025 randomized phase 3 study: outcomes by key baseline factors and prior therapy for nivolumab versus everolimus in advanced renal cell carcinoma. Eur Urol. 2017 Dec;72(6):962-971. Epub 2017 Mar 3. Erratum in: Eur Urol. 2018 Jan 3. [https://doi.org/10.1016/j.eururo.2017.02.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28262413/ PubMed]
-##'''Subgroup analysis:''' Tomita Y, Fukasawa S, Shinohara N, Kitamura H, Oya M, Eto M, Tanabe K, Saito M, Kimura G, Yonese J, Yao M, Uemura H. Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup 3-year follow-up analysis from the phase III CheckMate 025 study. Jpn J Clin Oncol. 2019 Jun 1;49(6):506-514. [https://academic.oup.com/jjco/article-abstract/49/6/506/5426435 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30941424/ PubMed]
-##'''Update:''' Motzer RJ, Escudier B, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Plimack ER, Procopio G, McDermott DF, Castellano D, Choueiri TK, Donskov F, Gurney H, Oudard S, Richardet M, Peltola K, Alva AS, Carducci M, Wagstaff J, Chevreau C, Fukasawa S, Tomita Y, Gauler TC, Kollmannsberger CK, Schutz FA, Larkin J, Cella D, McHenry MB, Saggi SS, Tannir NM. Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial. Cancer. 2020 Sep 15;126(18):4156-4167. Epub 2020 Jul 16. [https://doi.org/10.1002/cncr.33033 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8415096/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32673417/ PubMed]
-#'''METEOR:''' Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Géczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ; METEOR Investigators. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. Epub 2015 Sep 25. [https://doi.org/10.1056/NEJMoa1510016 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024539/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26406150/ PubMed] [https://clinicaltrials.gov/study/NCT01865747 NCT01865747]
-##'''Update:''' Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DY, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ; METEOR investigators. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-27. Epub 2016 Jun 5. [https://doi.org/10.1016/S1470-2045(16)30107-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27279544/ PubMed]
-##'''HRQoL analysis:''' Cella D, Escudier B, Tannir NM, Powles T, Donskov F, Peltola K, Schmidinger M, Heng DYC, Mainwaring PN, Hammers HJ, Lee JL, Roth BJ, Marteau F, Williams P, Baer J, Mangeshkar M, Scheffold C, Hutson TE, Pal S, Motzer RJ, Choueiri TK. Quality of life outcomes for cabozantinib versus everolimus in patients with metastatic renal cell carcinoma: METEOR phase III randomized trial. J Clin Oncol. 2018 Mar 10;36(8):757-764. Epub 2018 Jan 29. [https://doi.org/10.1200/JCO.2017.75.2170 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6804841/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29377755/ PubMed]
-##'''Update:''' Motzer RJ, Escudier B, Powles T, Scheffold C, Choueiri TK. Long-term follow-up of overall survival for cabozantinib versus everolimus in advanced renal cell carcinoma. Br J Cancer. 2018 May;118(9):1176-1178. Epub 2018 Mar 26. [https://doi.org/10.1038/s41416-018-0061-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943250/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29576624/ PubMed]
-#'''E7080-G000-205:''' Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-82. Epub 2015 Oct 22. [https://doi.org/10.1016/S1470-2045(15)00290-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26482279/ PubMed] [https://clinicaltrials.gov/study/NCT01136733 NCT01136733]
-##'''Update:''' Motzer RJ, Hutson TE, Ren M, Dutcus C, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. [https://doi.org/10.1016/S1470-2045(15)00543-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26758760/ PubMed]
-#'''RECORD-4:''' Motzer RJ, Alyasova A, Ye D, Karpenko A, Li H, Alekseev B, Xie L, Kurteva G, Kowalyszyn R, Karyakin O, Neron Y, Cosgriff T, Collins L, Brechenmacher T, Lin C, Morgan L, Yang L. Phase II trial of second-line everolimus in patients with metastatic renal cell carcinoma (RECORD-4). Ann Oncol. 2016 Mar;27(3):441-8. Epub 2015 Dec 17. [https://doi.org/10.1093/annonc/mdv612 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006123/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26681676/ PubMed] [https://clinicaltrials.gov/study/NCT01491672 NCT01491672]
-#'''CONCEPT<sub>RCC</sub>:''' Sheng X, Ye D, Zhou A, Yao X, Luo H, He Z, Wang Z, Zhao Y, Ji Z, Zou Q, He C, Guo J, Tu X, Liu Z, Shi B, Liu B, Chen P, Wei Q, Hu Z, Zhang Y, Jiang K, Zhou F, Wu D, Fu C, Li X, Wu B, Wang L, Qin S, Li G, Liu Y, Guo H, Chen K, Zhang D, Wang G, Ding L, Wang Y, Yuan X, Guo J. Efficacy and safety of vorolanib plus everolimus in metastatic renal cell carcinoma: A three-arm, randomised, double-blind, multicentre phase III study (CONCEPT). Eur J Cancer. 2023 Jan;178:205-215. Epub 2022 Nov 1. [https://doi.org/10.1016/j.ejca.2022.10.025 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36459768/ PubMed] [https://clinicaltrials.gov/study/NCT03095040 NCT03095040]
-==Everolimus & Lenvatinib {{#subobject:21039d|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:71ef67|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-| rowspan="2" |[https://doi.org/10.1016/S1470-2045(15)00290-9 Motzer et al. 2015 (E7080-G000-205)]
-<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-112-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-|-
-|} -->
-| rowspan="2" |2012-03-16 to 2013-06-19
-| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-RT-esc)
-|1. [[#Everolimus_monotherapy|Everolimus]]
-| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 14.6 vs 5.5 mo<br>(HR 0.40, 95% CI 0.24-0.68)
-|-
-|2. [[#Lenvatinib_monotherapy|Lenvatinib]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 14.6 vs 7.4 mo<br>(HR 0.66, 95% CI 0.30-1.10)
-|-
-|}
-<div class="toccolours" style="background-color:#fdcdac">
-====Prior treatment criteria====
-*[[:Category:VEGFR_inhibitors|VEGFR TKI]] treatment, with progression
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Everolimus (Afinitor)]] 5 mg PO once per day
-*[[Lenvatinib (Lenvima)]] 18 mg PO once per day
-'''Continued indefinitely'''
-</div></div>
-===References===
-#'''E7080-G000-205:''' Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-82. Epub 2015 Oct 22. [https://doi.org/10.1016/S1470-2045(15)00290-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26482279/ PubMed] [https://clinicaltrials.gov/study/NCT01136733 NCT01136733]
-##'''Update:''' Motzer RJ, Hutson TE, Ren M, Dutcus C, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. [https://doi.org/10.1016/S1470-2045(15)00543-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26758760/ PubMed]
-==Lenvatinib monotherapy {{#subobject:PYR3|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:PYV3|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-| rowspan="2" |[https://doi.org/10.1016/S1470-2045(15)00290-9 Motzer et al. 2015 (E7080-G000-205)]
-<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-113-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
-|-
-|} -->
-| rowspan="2" |2012-03-16 to 2013-06-19
-| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-RT-switch-ic)
-|1. [[#Everolimus_monotherapy|Everolimus]]
-| style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 7.4 vs 5.5 mo<br>(HR 0.61, 95% CI 0.38-0.98)
-|-
-|2. [[#Everolimus_.26_Lenvatinib | Everolimus & Lenvatinib]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Lenvatinib (Lenvima)]] 24 mg PO once per day
-'''Continued indefinitely'''
-</div></div>
-===References===
-#'''E7080-G000-205:''' Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-82. Epub 2015 Oct 22. [https://doi.org/10.1016/S1470-2045(15)00290-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26482279/ PubMed] [https://clinicaltrials.gov/study/NCT01136733 NCT01136733]
-##'''Update:''' Motzer RJ, Hutson TE, Ren M, Dutcus C, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. [https://doi.org/10.1016/S1470-2045(15)00543-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26758760/ PubMed]
-==Nivolumab monotherapy {{#subobject:pyr2|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 0.3 mg/kg q3wk {{#subobject:6d0807|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/JCO.2014.59.0703 Motzer et al. 2015 (CheckMate 010)]
-|2011-2012
-| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
-|1. [[#Nivolumab_monotherapy|Nivolumab]]; 2 mg/kg<br>2. [[#Nivolumab_monotherapy|Nivolumab]]; 10 mg/kg
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
-*[[Nivolumab (Opdivo)]] 0.3 mg/kg IV once on day 1
-'''21-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 2 mg/kg q3wk {{#subobject:e0b43a|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/JCO.2014.59.0703 Motzer et al. 2015 (CheckMate 010)]
-|2011-2012
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
-|1. [[#Nivolumab_monotherapy|Nivolumab]]; 0.3 mg/kg<br>2. [[#Nivolumab_monotherapy|Nivolumab]]; 10 mg/kg
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
-*[[Nivolumab (Opdivo)]] 2 mg/kg IV once on day 1
-'''21-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 3 mg/kg q2wk {{#subobject:pyv2|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5719487/ Motzer et al. 2015 (CheckMate 025)]
-<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-103-1 <span style="color:white;">ESMO-MCBS (5)</span>]'''
-|-
-|} -->
-|2012-2014
-| style="background-color:#1a9851" | Phase 3 (E-RT-switch-ooc)
-|[[#Everolimus_monotherapy_2|Everolimus]]
-| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 25 vs 19.6 mo<br>(HR 0.73, 98.5% CI 0.57-0.93)
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-''Note: On 2016-09-13 the [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm520871.htm FDA recommended] that dosing for this indication be changed to 240 mg with the same schedule based on updated pharmacokinetic data.''
-====Immunotherapy====
-*[[Nivolumab (Opdivo)]] 3 mg/kg IV over 60 minutes once on day 1
-'''14-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, 10 mg/kg q3wk {{#subobject:6f2515|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/JCO.2014.59.0703 Motzer et al. 2015 (CheckMate 010)]
-|2011-2012
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
-|1. [[#Nivolumab_monotherapy|Nivolumab]]; 0.3 mg/kg<br>2. [[#Nivolumab_monotherapy|Nivolumab]]; 2 mg/kg
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
-*[[Nivolumab (Opdivo)]] 10 mg/kg IV once on day 1
-'''21-day cycles'''
-</div></div>
-===References===
-#'''CheckMate 010:''' Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel TM, Harrison MR, Vaishampayan UN, Drabkin HA, George S, Logan TF, Margolin KA, Plimack ER, Lambert AM, Waxman IM, Hammers HJ. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol. 2015 May 1;33(13):1430-7. Epub 2014 Dec 1. [https://doi.org/10.1200/JCO.2014.59.0703 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806782/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25452452/ PubMed] [https://clinicaltrials.gov/study/NCT01354431 NCT01354431]
-#'''CheckMate 025:''' Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015 Nov 5;373(19):1803-13. Epub 2015 Sep 25. [https://doi.org/10.1056/NEJMoa1510665 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5719487/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26406148/ PubMed] [https://clinicaltrials.gov/study/NCT01668784 NCT01668784]
-##'''HRQoL analysis:''' Cella D, Grünwald V, Nathan P, Doan J, Dastani H, Taylor F, Bennett B, DeRosa M, Berry S, Broglio K, Berghorn E, Motzer RJ. Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimus in CheckMate 025: a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):994-1003. Epub 2016 Jun 6. Erratum in: Lancet Oncol. 2016 Jul;17 (7):e270. [https://doi.org/10.1016/S1470-2045(16)30125-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27283863/ PubMed]
-##'''Subgroup analysis:''' Escudier B, Sharma P, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Gurney H, Donskov F, Peltola K, Wagstaff J, Gauler TC, Ueda T, Zhao H, Waxman IM, Motzer RJ; CheckMate 025 investigators. CheckMate 025 randomized phase 3 study: outcomes by key baseline factors and prior therapy for nivolumab versus everolimus in advanced renal cell carcinoma. Eur Urol. 2017 Dec;72(6):962-971. Epub 2017 Mar 3. Erratum in: Eur Urol. 2018 Jan 3. [https://doi.org/10.1016/j.eururo.2017.02.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28262413/ PubMed]
-##'''Subgroup analysis:''' Tomita Y, Fukasawa S, Shinohara N, Kitamura H, Oya M, Eto M, Tanabe K, Saito M, Kimura G, Yonese J, Yao M, Uemura H. Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup 3-year follow-up analysis from the phase III CheckMate 025 study. Jpn J Clin Oncol. 2019 Jun 1;49(6):506-514. [https://academic.oup.com/jjco/article-abstract/49/6/506/5426435 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30941424/ PubMed]
-##'''Update:''' Motzer RJ, Escudier B, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Plimack ER, Procopio G, McDermott DF, Castellano D, Choueiri TK, Donskov F, Gurney H, Oudard S, Richardet M, Peltola K, Alva AS, Carducci M, Wagstaff J, Chevreau C, Fukasawa S, Tomita Y, Gauler TC, Kollmannsberger CK, Schutz FA, Larkin J, Cella D, McHenry MB, Saggi SS, Tannir NM. Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial. Cancer. 2020 Sep 15;126(18):4156-4167. Epub 2020 Jul 16. [https://doi.org/10.1002/cncr.33033 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8415096/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32673417/ PubMed]
-== Pazopanib monotherapy {{#subobject:443024|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:d6c07c|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.2008.21.6994 Hutson et al. 2009 (VEG102616)]
-|2005-10 to 2006-09
-| style="background-color:#91cf61" |Phase 2
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|[https://doi.org/10.1200/jco.2009.23.9764 Sternberg et al. 2010 (VEG105192)]
-|2006-04 to 2007-04
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[Renal_cell_carcinoma_-_null_regimens#Placebo_3|Placebo]]
-| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 9.2 vs 4.2 mo<br>(HR 0.46, 95% CI 0.34-0.62)
-|-
-|[https://doi.org/10.1016/j.clgc.2013.04.006 Hainsworth et al. 2013]
-|2008-2011
-| style="background-color:#91cf61" |Phase 2
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|}
-<div class="toccolours" style="background-color:#fdcdac">
-==== Prior treatment criteria====
-*VEG105192: Progression on 1 prior cytokine-based systemic therapy
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Pazopanib (Votrient)]] 800 mg PO once per day, given 1 hour before or 2 hours after meals
-'''Continued indefinitely'''
-</div>
-<div class="toccolours" style="background-color:#fff2ae">
-====Dose and schedule modifications====
-*Dose may be decreased to 600 mg or 400 mg PO once per day depending on tolerability
-</div></div>
-===References===
-#'''VEG102616:''' Hutson TE, Davis ID, Machiels JP, De Souza PL, Rottey S, Hong BF, Epstein RJ, Baker KL, McCann L, Crofts T, Pandite L, Figlin RA. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010 Jan 20;28(3):475-80. Epub 2009 Dec 14. [https://doi.org/10.1200/jco.2008.21.6994 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20008644/ PubMed] [https://clinicaltrials.gov/study/NCT00244764 NCT00244764]
-#'''VEG105192:''' Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. Epub 2010 Jan 25. [https://doi.org/10.1200/jco.2009.23.9764 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20100962/ PubMed] [https://clinicaltrials.gov/study/NCT00334282 NCT00334282]
-##'''Update:''' Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. 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 Apr;49(6):1287-96. Epub 2013 Jan 12. [https://doi.org/10.1016/j.ejca.2012.12.010 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23321547/ PubMed]
-#Hainsworth JD, Rubin MS, Arrowsmith ER, Khatcheressian J, Crane EJ, Franco LA. Pazopanib as second-line treatment after sunitinib or bevacizumab in patients with advanced renal cell carcinoma: a Sarah Cannon Oncology Research Consortium phase II trial. Clin Genitourin Cancer. 2013 Sep;11(3):270-5. Epub 2013 May 9. [https://doi.org/10.1016/j.clgc.2013.04.006 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23665131/ PubMed]
 ==Sorafenib monotherapy {{#subobject:6e18d8|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 1,519: / Line 751: @@
 #'''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. [https://doi.org/10.1200/JCO.2013.50.3961 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569683/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24297950/ PubMed] [https://clinicaltrials.gov/study/NCT00474786 NCT00474786]
-== Sunitinib monotherapy {{#subobject:f929da|Regimen=1}}==
+==Sunitinib monotherapy {{#subobject:f929da|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:955949|Variant=1}}===
@@ Line 1,531: / Line 763: @@
 |[https://doi.org/10.1200/JCO.2005.02.2574 Motzer et al. 2005 (RTKC-0511-014)]
 |2003
-| style="background-color:#91cf61" |Phase 2 (RT)
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|[https://jamanetwork.com/journals/jama/fullarticle/202955 Motzer et al. 2006 (A618-1006)]
-|2004
 | style="background-color:#91cf61" |Phase 2 (RT)
 | style="background-color:#d3d3d3" |
@@ Line 1,556: / Line 782: @@
 <div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-* RECORD-3: [[#Everolimus_monotherapy|Everolimus]]
+*RECORD-3: First-line [[#Everolimus_monotherapy|Everolimus]]
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
@@ Line 1,569: / Line 795: @@
 ===References===
 #'''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. [https://doi.org/10.1200/JCO.2005.02.2574 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16330672/ PubMed]
-#'''A618-1006:''' Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Merchan JR, Wilding G, Ginsberg MS, Bacik J, Kim ST, Baum CM, Michaelson MD. Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 2006 Jun 7;295(21):2516-24. [https://jamanetwork.com/journals/jama/fullarticle/202955 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16757724/ PubMed] [https://clinicaltrials.gov/study/NCT00077974 NCT00077974]
 #'''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. [https://doi.org/10.1016/S1470-2045%2809%2970162-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19615940/ PubMed] [https://clinicaltrials.gov/study/NCT00130897 NCT00130897]
 #'''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. [https://doi.org/10.1200/jco.2013.54.6911 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25049330/ PubMed] [https://clinicaltrials.gov/study/NCT00903175 NCT00903175]
-=Metastatic disease, third-line=
-==Sorafenib monotherapy {{#subobject:7b51ba|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:87cb7d|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" | Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719485/ Motzer et al. 2014 (GOLD-RCC)]
-|2011-03 to 2012-09
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Dovitinib_monotherapy_777|Dovitinib]]
-| style="background-color:#fee08b" |Might have inferior PFS
-|-
-|[https://doi.org/10.1016/S1470-2045(19)30735-1 Rini et al. 2019 (TIVO-3)]
-|2016-05-24 to 2017-08-14
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Tivozanib_monotherapy_2|Tivozanib]]
-| style="background-color:#fc8d59" |Seems to have inferior PFS
-|-
-|}
-''Note: GOLD should not be confused for the one with the same name in gastric cancer.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Sorafenib (Nexavar)]] 400 mg PO twice per day
-'''Continued indefinitely'''
-</div></div>
-===References===
-#'''GOLD:''' Motzer RJ, Porta C, Vogelzang NJ, Sternberg CN, Szczylik C, Zolnierek J, Kollmannsberger C, Rha SY, Bjarnason GA, Melichar B, De Giorgi U, Grünwald V, Davis ID, Lee JL, Esteban E, Urbanowitz G, Cai C, Squires M, Marker M, Shi MM, Escudier B. Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Mar;15(3):286-96. Epub 2014 Feb 17. [https://doi.org/10.1016/S1470-2045(14)70030-0 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24556040/ PubMed] [https://clinicaltrials.gov/study/NCT01223027 NCT01223027]
-#'''TIVO-3:''' Rini BI, Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, Verzoni E, Needle MN, McDermott DF. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020 Jan;21(1):95-104. Epub 2019 Dec 3. [https://doi.org/10.1016/S1470-2045(19)30735-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31810797/ PubMed] [https://clinicaltrials.gov/study/NCT02627963 NCT02627963]
-##'''Update:''' Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, Verzoni E, Needle MN, Powers D, McDermott DF, Rini BI. 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 Dec;78(6):783-785. Epub 2020 Sep 13. [https://doi.org/10.1016/j.eururo.2020.08.007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32938569/ PubMed]
-==Tivozanib monotherapy {{#subobject:h7qut0|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 1.34 mg/day {{#subobject:1ug7ad|Variant=1}}===
-{| class="wikitable sortable" style="color:white; background-color:#404040"
-|<small>'''FDA-recommended dose'''</small>
-|-
-|}
-''Note: this is not the dose reported in the manuscript.''
-<div class="toccolours" style="background-color:#b3e2cd">
-==== Targeted therapy====
-*[[Tivozanib (Fotivda)]] 1.34 mg PO once per day on days 1 to 21
-'''28-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 1.5 mg/day {{#subobject:1yq32d|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1016/S1470-2045(19)30735-1 Rini et al. 2019 (TIVO-3)]
-<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-268-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
-|-
-|} -->
-|2016-05-24 to 2017-08-14
-| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
-|[[#Sorafenib_monotherapy_3|Sorafenib]]
-| style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.6 vs 3.9 mo<br>(HR 0.73, 95% CI 0.56-0.94)
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Tivozanib (Fotivda)]] 1.5 mg PO once per day on days 1 to 21
-'''28-day cycles'''
-</div></div>
-===References===
-#'''TIVO-3:''' Rini BI, Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, Verzoni E, Needle MN, McDermott DF. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020 Jan;21(1):95-104. Epub 2019 Dec 3. [https://doi.org/10.1016/S1470-2045(19)30735-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31810797/ PubMed] [https://clinicaltrials.gov/study/NCT02627963 NCT02627963]
-##'''Update:''' Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, Verzoni E, Needle MN, Powers D, McDermott DF, Rini BI. 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 Dec;78(6):783-785. Epub 2020 Sep 13. [https://doi.org/10.1016/j.eururo.2020.08.007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32938569/ PubMed]
 [[Category:Renal cell carcinoma regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Genitourinary cancers]]

Difference between revisions of "Renal cell carcinoma"

Latest revision as of 17:53, 23 June 2024

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