Revision as of 18:34, 15 September 2016

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14 regimens on this page 22 variants on this page

Metastatic disease, first-line

Axitinib (Inlyta)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Hutson et al. 2013	Phase III	32%	Sorafenib	15%

Chemotherapy

Axitinib (Inlyta) as follows:
- 5 mg PO BID for at least 2 weeks
- Then if tolerated and BP not greater than 150/90, increased to 7 mg PO BID
- Then if tolerated and BP not greater than 150/90, increased to 10 mg PO BID
- Dose can be reduced to 2 to 3 mg PO BID if needed based on tolerability

References

Hutson TE, Lesovoy V, Al-Shukri S, Stus VP, Lipatov ON, Bair AH, Rosbrook B, Chen C, Kim S, Vogelzang NJ. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1287-94. Epub 2013 Oct 25. link to original article PubMed

Bevacizumab (Avastin)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Bukowski et al. 2007	Randomized Phase II	13%	Bevacizumab & Erlotinib	14%

Chemotherapy

Bevacizumab (Avastin) 10 mg/kg IV over 90 minutes once every 2 weeks
- Can subsequently be reduced to 60 and 30 minute infusions as tolerated

Given for up to 104 weeks, until progression of disease, or unacceptable toxicity

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. link to original article contains verified protocol PubMed

Bevacizumab & Erlotinib

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Regimen

Study	Evidence	Comparator
Bukowski et al. 2007	Randomized Phase II	Bevacizumab

Chemotherapy

Bevacizumab (Avastin) 10 mg/kg IV over 90 minutes once every 2 weeks
- Can subsequently be reduced to 60 and 30 minute infusions as tolerated
Erlotinib (Tarceva) 150 mg PO once per day

Given for up to 104 weeks, until progression of disease, or unacceptable toxicity

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. link to original article contains verified protocol PubMed

Bevacizumab & Interferon alfa-2a

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Regimen

Study	Evidence	Comparator
Escudier et al. 2007 (AVOREN)	Phase III	Interferon alfa-2a
Rini et al. 2008 (CALGB 90206)	Phase III	Interferon alfa-2a

Chemoimmunotherapy

Bevacizumab (Avastin) 10 mg/kg IV once every 2 weeks
Interferon alfa-2a (Roferon-A) 9 million units SC 3 times per week
- Dose can be reduced to 3 or 6 million units SC 3 times per week based on tolerability

Interferon alfa-2a given for up to 52 weeks, until progression of disease, or unacceptable toxicity; bevacizumab given until progression of disease or unacceptable toxicity

References

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. link to original article PubMed
1. 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. link to original article contains verified protocol PubMed
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. link to original article PubMed
1. 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. link to original article PubMed

Erlotinib (Tarceva)

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Regimen

Study	Evidence	ORR
Gordon et al. 2009 (SWOG S0317)	Phase II	11% (95% CI 3-24%)

Chemotherapy

Erlotinib (Tarceva) 150 mg PO once per day, given 1 hour before or 2 hours after meals

Given until progression of disease or unacceptable toxicity

References

Gordon MS, Hussey M, Nagle RB, Lara PN Jr, Mack PC, Dutcher J, Samlowski W, Clark JI, Quinn DI, Pan CX, Crawford D. Phase II study of erlotinib in patients with locally advanced or metastatic papillary histology renal cell cancer: SWOG S0317. J Clin Oncol. 2009 Dec 1;27(34):5788-93. Epub 2009 Nov 2. link to original article contains verified protocol PubMed

Everolimus (Afinitor)

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Regimen

Study	Evidence	Comparator
Motzer et al. 2014 (RECORD-3)	Randomized Phase II	Sunitinib
Armstrong et al. 2016 (ASPEN)	Randomized Phase II	Sunitinib

Chemotherapy

Everolimus (Afinitor) 10 mg PO once per day
- Dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability

Given until progression of disease or unacceptable toxicity

Patients in RECORD-3 were pre-assigned to receive sunitinib at the time of progression.

References

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 PubMed
Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, Lusk CM, Oberg S, George DJ. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016 Mar;17(3):378-88. Epub 2016 Jan 13. link to original article PubMed

Gemcitabine & Doxorubicin

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Regimen

Study	Evidence
Haas et al. 2012 (ECOG 8802)	Phase II

Patients had disease with sarcomatoid features.

Chemotherapy

Gemcitabine (Gemzar) 1500 mg/m² IV over 30 minutes once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV push once on day 1

14-day cycles, given until cumulative doxorubicin dose of 300 to 450 mg/m² (depending on cardiac function), progression of disease, or unacceptable toxicity

Supportive medications

One of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on starting on day 2 or 3, given until day 10
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2

References

Haas NB, Lin X, Manola J, Pins M, Liu G, McDermott D, Nanus D, Heath E, Wilding G, Dutcher J. A phase II trial of doxorubicin and gemcitabine in renal cell carcinoma with sarcomatoid features: ECOG 8802. Med Oncol. 2012 Jun;29(2):761-7. Epub 2011 Feb 6. link to original article contains verified protocol PubMed

Gemcitabine & Sunitinib

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Regimen #1

Study	Evidence
Michaelson et al. 2015	Phase II

Patients had disease with sarcomatoid features.

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 14

21-day cycles

Regimen #2

Study	Evidence
Pandya et al. 2011	Retrospective

Chemotherapy

Gemcitabine (Gemzar) 750 mg/m² IV over 90 minutes once per day on days 1 & 8
Sunitinib (Sutent) 37.5 mg PO once per day on days 2 to 15

21-day cycles

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. link to original article contains verified protocol PubMed
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

High-dose (HD) IL-2

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Example orders

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

Regimen #1

Study	Evidence	Comparator
McDermott et al. 2005	Phase III	Subcutaneous IL-2 & Interferon

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

28-day cycle for up to 3 cycles

Supportive medications

Ciprofloxacin (Cipro) 250 mg PO BID 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"

Regimen #2

Study	Evidence	Comparator
Yang et al. 2003	Phase III	Intravenous low-dose IL-2 Subcutaneous low-dose IL-2

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 #3

Study	Evidence
Klapper et al. 2008	Retrospective

Immunotherapy

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, IL-2 - Aldesleukin (Proleukin) 720,000 units/kg IV every 8 hours for up to 12 doses is given again

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)

Supportive medications

"Routine administration of antipyretics, anti-inflammatories, antiemetics, antidiarrheals, and H2 antagonists."

References

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 link to PMC article contains verified protocol 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 verified protocol 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. link to original article contains verified protocol PubMed

Low-dose (LD) IL-2

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Regimen #1, Intravenous

Study	Evidence	Comparator
Yang et al. 2003	Phase III	High-dose IL-2 Subcutaneous low-dose IL-2

Immunotherapy

IL-2 - Aldesleukin (Proleukin) 72,000 units/kg IV every 8 hours for up to 15 doses
- Then after 7 to 10 days of rest, IL-2 - Aldesleukin (Proleukin) 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 #2, Subcutaneous

Study	Evidence	Comparator
Yang et al. 2003	Phase III	High-dose IL-2 Intravenous low-dose IL-2

Immunotherapy

IL-2 - Aldesleukin (Proleukin) 250,000 units/kg SC once per day for 5 days on week 1
- Then IL-2 - Aldesleukin (Proleukin) 125,000 units/kg SC once per day for 5 days per week during weeks 2 to 6

8-week cycle for up to 2 cycles

References

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 verified protocol PubMed

Interferon alfa-2a (Roferon-A)

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Regimen #1

Study	Evidence	Comparator
Motzer et al. 2007	Phase III	Sunitinib

Immunotherapy

Interferon alfa-2a (Roferon-A) as follows:
- Week 1: 3 million units SC 3 times per week
- Week 2 (if prior dose tolerated): 6 million units SC 3 times per week
- Week 3 onwards (if prior dose tolerated): 9 million units SC 3 times per week

Given until progression of disease or unacceptable toxicity

Regimen #2

Study	Evidence	Comparator
Hudes et al. 2007 (ARCC)	Phase III	Interferon alfa-2a & Temsirolimus Temsirolimus

Immunotherapy

Interferon alfa-2a (Roferon-A) as follows:
- Week 1: 3 million units SC 3 times per week
- Week 2 (if prior dose tolerated): 9 million units SC 3 times per week
- Week 3 onwards (if prior dose tolerated): 18 million units SC 3 times per week
- If higher doses cannot be tolerated, highest tolerable doses of 3, 4.5, or 6 million units can be used

Regimen #3

Study	Evidence	Comparator
Escudier et al. 2007 (AVOREN)	Phase III	Bevacizumab & Interferon alfa-2a
Rini et al. 2008 (CALGB 90206)	Phase III	Bevacizumab & Interferon alfa-2a
Escudier et al. 2009	Randomized Phase II	Sorafenib

Immunotherapy

Interferon alfa-2a (Roferon-A) 9 million units SC 3 times per week
- Dose can be reduced to 3 or 6 million units SC 3 times per week based on tolerability

Interferon alfa-2a given for up to 52 weeks, until progression of disease, or unacceptable toxicity

References

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. link to original article contains verified protocol PubMed
1. 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. link to original article contains verified protocol PubMed content property of HemOnc.org
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 verified protocol PubMed
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. link to original article PubMed
1. 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. link to original article contains verified protocol PubMed
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. link to original article PubMed
1. 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. link to original article PubMed
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. link to original article PubMed

Pazopanib (Votrient)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Hutson et al. 2010	Phase II
Sternberg et al. 2010 (VEG105192)	Phase III	30% (95% CI 25-36%)	Placebo	3% (95% CI 0-6%)
Motzer et al. 2013	Phase III	31% (95% CI 27-34%)	Sunitinib	25% (95% CI 21-28%)

Chemotherapy

Pazopanib (Votrient) 800 mg PO once per day, given 1 hour before or 2 hours after meals
- Dose may be decreased to 600 mg or 400 mg PO once per day depending on tolerability

Given until progression of disease, unacceptable toxicity, death, or withdrawal of consent

References

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. link to original article contains verified protocol PubMed
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. link to original article contains verified protocol PubMed
1. 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. link to original article contains verified protocol PubMed
Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. link to original article contains verified protocol PubMed
1. Update: Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014 May 1;370(18):1769-70. link to letter PubMed

Placebo

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Regimen

Study	Evidence	Comparator
Sternberg et al. 2010 (VEG105192)	Phase III	Pazopanib

No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.

References

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. link to original article contains verified protocol PubMed
1. 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. link to original article contains verified protocol PubMed

Regorafenib (Stivarga)

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Regimen

Study	Evidence	ORR
Eisen et al. 2012	Phase II	40% (90% CI 28-53%)

Chemotherapy

Regorafenib (Stivarga) 160 mg PO once per day on days 1 to 21, given while fasting or after a light meal

28-day cycles, given until progression of disease or unacceptable toxicity

References

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. link to original article contains verified protocol PubMed

Sorafenib (Nexavar)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Escudier et al. 2009	Randomized Phase II		Interferon alfa-2a
Stadler et al. 2010 (ARCCS)	Non-randomized
Hutson et al. 2013	Phase III	15%	Axitinib	32%

Chemotherapy

Sorafenib (Nexavar) 400 mg PO BID
- Can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity

Continued until progression or intolerance

References

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. link to original article PubMed
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
Hutson TE, Lesovoy V, Al-Shukri S, Stus VP, Lipatov ON, Bair AH, Rosbrook B, Chen C, Kim S, Vogelzang NJ. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1287-94. Epub 2013 Oct 25. link to original article PubMed

Sunitinib (Sutent)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Motzer et al. 2007	Phase III	31%	Interferon alfa-2a	6%
Choueiri et al. 2008	Non-randomized	10%
Gore et al. 2009	Non-randomized	17%
Motzer et al. 2013	Phase III	25% (95% CI 21-28%)	Pazopanib	31% (95% CI 27-34%)
Motzer et al. 2014 (RECORD-3)	Randomized Phase II		Everolimus
Armstrong et al. 2016 (ASPEN)	Randomized Phase II		Everolimus

Chemotherapy

Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
- Dose may be decreased to Sunitinib (Sutent) 37.5 mg or 25 mg PO once per day depending on tolerability

42-day cycles, given until progression of disease or unacceptable toxicity

References

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. link to original article contains verified protocol PubMed
1. 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. link to original article contains verified protocol PubMed
Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, Zhou M, Rini BI, Bukowski RM, Escudier B. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol. 2008 Jan 1;26(1):127-31. link to original article PubMed
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 verified protocol PubMed
Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. link to original article contains verified protocol PubMed
1. Update: Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014 May 1;370(18):1769-70. link to letter PubMed
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 PubMed
Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, Lusk CM, Oberg S, George DJ. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016 Mar;17(3):378-88. Epub 2016 Jan 13. link to original article PubMed

Temsirolimus (Torisel)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Hudes et al. 2007	Phase III	9% (95% CI 5-12%)	Interferon alfa-2a Interferon alfa-2a & Temsirolimus	5% (95% CI 2-8%) 8% (95% CI 4-12%)

Chemotherapy

Temsirolimus (Torisel) 25 mg IV over 30 minutes once per week

Supportive medications

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

References

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 verified protocol PubMed

Metastatic disease, second-line

Axitinib (Inlyta)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Rini et al. 2011 (AXIS)	Phase III	19% (95% CI 15-24%)	Sorafenib	9% (95% CI 7-13%)

Chemotherapy

Axitinib (Inlyta) as follows:
- 5 mg PO BID for at least 2 weeks
- Then if tolerated and BP not greater than 150/90, increased to 7 mg PO BID
- Then if tolerated and BP not greater than 150/90, increased to 10 mg PO BID
- Dose can be reduced to 2 to 3 mg PO BID if needed based on tolerability

References

Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. link to original article contains verified protocol PubMed
1. Update: Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552-62. Epub 2013 Apr 15. link to original article contains verified protocol PubMed

Cabozantinib (Cabometyx)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy
Choueiri et al. 2015 (METEOR)	Phase III	21% (95% CI 16-28%)	Everolimus	5% (95% CI 2-9%)	Improved PFS

Patients had progressed after VEGFR TKI treatment.

Chemotherapy

Cabozantinib (Cabometyx) 60 mg PO once per day
- At least 2 hours before or 1 hour after meals according to the Cabozantinib (Cabometyx) package insert

Used as long as clinical benefit was perceived or unacceptable toxicity

References

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. link to original article contains verified protocol PubMed
1. Update: ASCO 2016 Abstract 4506

Everolimus (Afinitor)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Motzer et al. 2008 (RECORD-1)	Phase III	1%	Placebo	0%
Motzer et al. 2014 (RECORD-3)	Randomized Phase II		Sunitinib
Motzer et al. 2015 (CheckMate 025)	Phase III	5%	Nivolumab	25%
Choueiri et al. 2015 (METEOR)	Phase III	5% (95% CI 2-9%)	Cabozantinib	21% (95% CI 16-28%)
Motzer et al. 2015	Randomized Phase II		Everolimus & Lenvatinib Lenvatinib

Patients in RECORD-1 and METEOR had progressed after VEGFR TKI treatment. Patients in RECORD-3 were pre-assigned to receive sunitinib in the first-line. 72% of patients in Checkmate 025 had anti-angiogenic therapy prior to progression.

Chemotherapy

Everolimus (Afinitor) 10 mg PO once per day
- Dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability

Given until progression of disease or unacceptable toxicity.

References

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. link to original article contains verified protocol PubMed
1. 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. link to original article contains verified protocol PubMed
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 PubMed
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 Sep 25. link to original article contains verified protocol PubMed
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. link to original article contains verified protocol PubMed
1. Update: ASCO 2016 Abstract 4506
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. link to original article contains verified protocol PubMed
1. Update: Motzer RJ, Hutson TE, Ren M3, Dutcus C3, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. link to original article PubMed

Everolimus & Lenvatinib

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Motzer et al. 2015	Randomized Phase II	43% (95% CI 29-58%)	Everolimus Lenvatinib	6% (95% CI 1-17%) 27% (95% CI 16-41%)

Patients had progressed after VEGFR TKI treatment.

Chemotherapy

Everolimus (Afinitor) 5 mg PO once per day
Lenvatinib (Lenvima) 18 mg PO once per day

Continued until progression or unacceptable toxicity

References

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. link to original article contains verified protocol PubMed
1. Update: Motzer RJ, Hutson TE, Ren M3, Dutcus C3, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. link to original article PubMed

Lenvatinib (Lenvima)

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Regimen

Study	Evidence	Comparator
Motzer et al. 2015	Randomized Phase II	Everolimus Everolimus & Lenvatinib

Note: The 5/13/2016 FDA approved use of Lenvatinib (Lenvima) is in combination with Everolimus (Afinitor). In Motzer et al. 2015, "single-agent lenvatinib significantly prolonged progression-free survival compared with everolimus alone. Everolimus & levatinib had a non-statistically signficant improved PFS compared to single-agent levatinib.

Chemotherapy

Lenvatinib (Lenvima) 24 mg PO once per day

Continued until progression or unacceptable toxicity

References

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. link to original article contains verified protocol PubMed
1. Update: Motzer RJ, Hutson TE, Ren M3, Dutcus C3, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. link to original article PubMed

Nivolumab (Opdivo)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Motzer et al. 2015 (CheckMate 025)	Phase III	25%	Everolimus	5%

Immunotherapy

Nivolumab (Opdivo) 3 mg/kg IV over 60 minutes on day 1

14-day cycles

References

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. link to original article contains verified protocol PubMed

Pazopanib (Votrient)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Hutson et al. 2010	Phase II
Sternberg et al. 2010 (VEG105192)	Phase III	30% (95% CI 25-36%)	Placebo	3% (95% CI 0-6%)
Hainsworth et al. 2013	Phase II

Chemotherapy

Pazopanib (Votrient) 800 mg PO once per day, given 1 hour before or 2 hours after meals
- Dose may be decreased to 600 mg or 400 mg PO once per day depending on tolerability

Given until progression of disease, unacceptable toxicity, death, or withdrawal of consent

References

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. link to original article contains verified protocol PubMed
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. link to original article contains verified protocol PubMed
1. 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. link to original article contains verified protocol 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. link to original article contains protocol PubMed

Placebo

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Regimen

Study	Evidence	Comparator
Escudier et al. 2007 (TARGET)	Phase III	Sorafenib
Motzer et al. 2008 (RECORD-1)	Phase III	Everolimus
Sternberg et al. 2010 (VEG105192)	Phase III	Pazopanib

No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.

References

Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. Erratum in: N Engl J Med. 2007 Jul 12;357(2):203. link to original article contains verified protocol PubMed
1. Update: Hutson TE, Bellmunt J, Porta C, Szczylik C, Staehler M, Nadel A, Anderson S, Bukowski R, Eisen T, Escudier B; Sorafenib TARGET Clinical Trial Group. Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. Eur J Cancer. 2010 Sep;46(13):2432-40. Epub 2010 Jul 23. link to original article contains verified protocol PubMed
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. link to original article contains verified protocol PubMed
1. 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. link to original article contains verified protocol PubMed
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. link to original article contains verified protocol PubMed
1. 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. link to original article contains verified protocol PubMed

Sorafenib (Nexavar)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Escudier et al. 2007 (TARGET)	Phase III	10%	Placebo	2%
Stadler et al. 2010 (ARCCS)	Non-randomized
Beck et al. 2011 (EU-ARCCS)	Non-randomized
Rini et al. 2011 (AXIS)	Phase III	9% (95% CI 7-13%)	Axitinib	19% (95% CI 15-24%)

Chemotherapy

Sorafenib (Nexavar) 400 mg PO BID
- Can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity

Continued until progression or intolerance

References

Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. Erratum in: N Engl J Med. 2007 Jul 12;357(2):203. link to original article contains verified protocol PubMed
1. Update: Hutson TE, Bellmunt J, Porta C, Szczylik C, Staehler M, Nadel A, Anderson S, Bukowski R, Eisen T, Escudier B; Sorafenib TARGET Clinical Trial Group. Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. Eur J Cancer. 2010 Sep;46(13):2432-40. Epub 2010 Jul 23. link to original article contains verified protocol PubMed
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. link to original article PubMed
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
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 verified protocol PubMed
Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. link to original article contains verified protocol PubMed
1. Update: Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552-62. Epub 2013 Apr 15. link to original article contains verified protocol PubMed

Sunitinib (Sutent)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR
Gore et al. 2009	Non-randomized	17%
Motzer et al. 2014 (RECORD-3)	Randomized Phase II		Everolimus

Chemotherapy

Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
- Dose may be decreased to Sunitinib (Sutent) 37.5 mg or 25 mg PO once per day depending on tolerability

42-day cycles, given until progression of disease or unacceptable toxicity

References

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 verified protocol PubMed
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 PubMed

Metastatic disease, third-line

Sorafenib (Nexavar)

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Regimen

Study	Evidence	Comparator
Motzer et al. 2014	Phase III	Dovitinib (TKI-258)

Chemotherapy

Sorafenib (Nexavar) 400 mg PO BID

References

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. link to original article contains protocol PubMed

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-|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
+|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
-<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
+<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
 |}
 {{TOC limit|limit=3}}
-=Metastatic disease=
+=Metastatic disease, first-line=
 ==Axitinib (Inlyta) {{#subobject:e83fa|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
@@ Line 24: / Line 24: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
-|Pt Population
-|-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961613-9/fulltext Rini et al. 2011 (AXIS)]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|19% (95% CI 15-24%)
-|[[Renal_cancer#Sorafenib_.28Nexavar.29|Sorafenib]]
-|9% (95% CI 7-13%)
-|Treatment exposed (sunitinib, cytokines)
 |-
 |[http://www.sciencedirect.com/science/article/pii/S1470204513704650 Hutson et al. 2013]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |32%
 |[[Renal_cancer#Sorafenib_.28Nexavar.29|Sorafenib]]
 |15%
-|Treatment naive
 |-
 |}
 ====Chemotherapy====
-*[[Axitinib (Inlyta)]] 5 mg PO BID for at least 2 weeks
+*[[Axitinib (Inlyta)]] as follows:
-**Then if tolerated and BP not greater than 150/90, increased to [[Axitinib (Inlyta)]] 7 mg PO BID
+**5 mg PO BID for at least 2 weeks
-***Then if tolerated and BP not greater than 150/90, increased to [[Axitinib (Inlyta)]] 10 mg PO BID
+**Then if tolerated and BP not greater than 150/90, increased to 7 mg PO BID
+**Then if tolerated and BP not greater than 150/90, increased to 10 mg PO BID
 **Dose can be reduced to 2 to 3 mg PO BID if needed based on tolerability
 ===References===
-# Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961613-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22056247 PubMed]
-## '''Update:''' Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552-62. Epub 2013 Apr 15. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70093-7/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23598172 PubMed]
 # Hutson TE, Lesovoy V, Al-Shukri S, Stus VP, Lipatov ON, Bair AH, Rosbrook B, Chen C, Kim S, Vogelzang NJ. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1287-94. Epub 2013 Oct 25. [http://www.sciencedirect.com/science/article/pii/S1470204513704650 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24206640 PubMed]
@@ Line 74: / Line 54: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
-|Pt Population
 |-
 |[http://jco.ascopubs.org/content/25/29/4536.full Bukowski et al. 2007]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |13%
 |[[Renal_cancer#Bevacizumab_.26_Erlotinib|Bevacizumab & Erlotinib]]
 |14%
-|Treatment naive
 |-
 |}
@@ Line 110: / Line 83: @@
 |-
 |[http://jco.ascopubs.org/content/25/29/4536.full Bukowski et al. 2007]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[Renal_cancer#Bevacizumab_.28Avastin.29|Bevacizumab]]
 |-
@@ Line 141: / Line 109: @@
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)61904-7/abstract Escudier et al. 2007 (AVOREN)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
 |-
 |[http://jco.ascopubs.org/content/26/33/5422.long Rini et al. 2008 (CALGB 90206)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
 |-
@@ Line 171: / Line 129: @@
 # 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. [http://jco.ascopubs.org/content/26/33/5422.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18936475 PubMed]
 ## '''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. [http://jco.ascopubs.org/content/28/13/2137.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20368558 PubMed]
-==Cabozantinib (Cabometyx) {{#subobject:pyr1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
-===Regimen {{#subobject:pyv1|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|[[Overall response rate|'''ORR''']]
-|'''Comparator'''
-|Comparator [[Overall response rate|'''ORR''']]
-|Pt Population
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
-|-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa1510016 Choueiri et al. 2015 (METEOR)]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|21% (95% CI 16-28%)
-|[[#Everolimus_.28Afinitor.29|Everolimus]]
-|5% (95% CI 2-9%)
-|Progressed after VEGFR TKI tx
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Improved PFS</span>
-|-
-|}
-====Chemotherapy====
-*[[Cabozantinib (Cabometyx)]] 60 mg PO once per day
-**At least 2 hours before or 1 hour after meals according to the [https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf Cabozantinib (Cabometyx) package insert]
-'''Used as long as clinical benefit was perceived or unacceptable toxicity'''
-===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1510016 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26406150 PubMed]
-## '''Update:''' ASCO 2016 Abstract 4506
 ==Erlotinib (Tarceva) {{#subobject:862d0a|Regimen=1}}==
@@ Line 228: / Line 142: @@
 |-
 |[http://jco.ascopubs.org/content/27/34/5788.long Gordon et al. 2009 (SWOG S0317)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |11% (95% CI 3-24%)
 |-
@@ Line 240: / Line 149: @@
 *[[Erlotinib (Tarceva)]] 150 mg PO once per day, given 1 hour before or 2 hours after meals
-‘’’Given until progression of disease or unacceptable toxicity'''
+'''Given until progression of disease or unacceptable toxicity'''
 ===References===
@@ Line 254: / Line 163: @@
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|[[Overall response rate|'''ORR''']]
 |'''Comparator'''
-|Comparator [[Overall response rate|'''ORR''']]
-|Pt Population
-|-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961039-9/fulltext Motzer et al. 2008 (RECORD-1)]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|1%
-|[[Renal_cancer#Placebo|Placebo]]
-|0%
-|Progessed after VEGFR TKI tx
 |-
 |[http://jco.ascopubs.org/content/32/25/2765.long Motzer et al. 2014 (RECORD-3)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
-|
 |[[Renal_cancer#Sunitinib_.28Sutent.29|Sunitinib]]
-|
-|
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa1510665 Motzer et al. 2015 (CheckMate 025)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00515-X/abstract Armstrong et al. 2016 (ASPEN)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
+|[[Renal_cancer#Sunitinib_.28Sutent.29|Sunitinib]]
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|5%
-|[[Renal_cancer#Nivolumab_.28Opdivo.29|Nivolumab]]
-|25%
-|Mixed pop; 72% had anti-angiogenic therapy
-|-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa1510016 Choueiri et al. 2015 (METEOR)]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|5% (95% CI 2-9%)
-|[[#Cabozantinib_.28Cabometyx.29|Cabozantinib]]
-|21% (95% CI 16-28%)
-|Progressed after VEGFR TKI tx
-|-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext Motzer et al. 2015]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
-|
-|[[#Everolimus_.26_Lenvatinib | Everolimus & Lenvatinib]]<br>[[#Lenvatinib_.28Lenvima.29|Lenvatinib]]
-|
-|
 |-
 |}
@@ Line 324: / Line 178: @@
 **Dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability
-'''Given until progression of disease or unacceptable toxicity.'''
+'''Given until progression of disease or unacceptable toxicity'''
+''Patients in '''RECORD-3''' were pre-assigned to receive [[#Sunitinib_.28Sutent.29_2|sunitinib]] at the time of progression.''
 ===References===
-# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961039-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18653228 PubMed]
-## '''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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25219/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20549832 PubMed]
 <!-- # '''Abstract:''' Robert John Motzer, Carlos H. Barrios, Tae Min Kim, Silvia Falcon, Thomas Cosgriff, W. Graydon Harker, Kenneth B. Pittman, Roberto Sabbatini, Sun Young Rha, Thomas W. Flaig, Ray D. Page, Sevil E. Bavbek, J. Thaddeus Beck, Poulam M Patel, Edward Schiff, Alexandra Vaury, Julie Niolat, Sven Gogov, Ozlem Anak, Jennifer Knox. Record-3: Phase II randomized trial comparing sequential first-line everolimus (EVE) and second-line sunitinib (SUN) versus first-line SUN and second-line EVE in patients with metastatic renal cell carcinoma (mRCC). 2013 ASCO Annual Meeting abstract 4504. [http://meetinglibrary.asco.org/content/113103-132 link to abstract] -->
 # 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. [http://jco.ascopubs.org/content/32/25/2765.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/25049330 PubMed]
-# 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 Sep 25. [http://www.nejm.org/doi/full/10.1056/NEJMoa1510665 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26406148 PubMed]
+# Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, Lusk CM, Oberg S, George DJ. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016 Mar;17(3):378-88. Epub 2016 Jan 13. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00515-X/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26794930 PubMed]
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1510016 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26406150 PubMed]
-## '''Update:''' ASCO 2016 Abstract 4506
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26482279 PubMed]
-## '''Update:''' Motzer RJ, Hutson TE, Ren M3, Dutcus C3, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00543-4/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26758760 PubMed]
-==Everolimus & Lenvatinib {{#subobject:21039d|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
-===Regimen {{#subobject:71ef67|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|[[Overall response rate|'''ORR''']]
-|'''Comparator'''
-|Comparator [[Overall response rate|'''ORR''']]
-|Pt Population
-|-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/abstract Motzer et al. 2015]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
-|43% (95% CI 29-58%)
-|[[#Everolimus_.28Afinitor.29|Everolimus]]<br> [[#Lenvatinib_.28Lenvima.29|Lenvatinib]]
-|6% (95% CI 1-17%)<br>27% (95% CI 16-41%)
-|progressed after VEGFR TKI tx
-|-
-|}
-====Chemotherapy====
-*[[Everolimus (Afinitor)]] 5 mg PO once per day
-*[[Lenvatinib (Lenvima)]] 18 mg PO once per day
-'''Continued until progression or unacceptable toxicity'''
-===References===
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26482279 PubMed]
-## '''Update:''' Motzer RJ, Hutson TE, Ren M3, Dutcus C3, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00543-4/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26758760 PubMed]
 ==Gemcitabine & Doxorubicin {{#subobject:bad0b3|Regimen=1}}==
@@ Line 385: / Line 198: @@
 |-
 |[http://www.springerlink.com/content/dnk52234n2567m5h/?MUD=MP Haas et al. 2012 (ECOG 8802)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+''Patients had disease with sarcomatoid features.''
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 1500 mg/m<sup>2</sup> IV over 30 minutes once on day 1
@@ Line 418: / Line 227: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1002/cncr.29503/abstract Michaelson et al. 2015]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
 ''Patients had disease with sarcomatoid features.''
 ====Chemotherapy====
@@ Line 440: / Line 243: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2011.10096.x/full Pandya et al. 2011]
-|<span
+|style="background-color:#ff0000"|Retrospective
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Retrospective</span>
 |-
 |}
@@ Line 473: / Line 271: @@
 |-
 |[http://jco.ascopubs.org/content/23/1/133.long McDermott et al. 2005]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |Subcutaneous IL-2 & Interferon
 |-
@@ Line 504: / Line 297: @@
 |-
 |[http://jco.ascopubs.org/content/21/16/3127.long Yang et al. 2003]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#Low-dose_.28LD.29_IL-2|Intravenous low-dose IL-2]]<br> [[Renal_cancer#Low-dose_.28LD.29_IL-2|Subcutaneous low-dose IL-2]]
 |-
@@ Line 525: / Line 313: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1002/cncr.23552/full Klapper et al. 2008]
-|<span
+|style="background-color:#ff0000"|Retrospective
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Retrospective</span>
 |-
 |}
@@ Line 543: / Line 326: @@
 ===References===
-# 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. [http://jco.ascopubs.org/content/21/16/3127.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12915604 PubMed]
+# 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. [http://jco.ascopubs.org/content/21/16/3127.long link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275327/ link to PMC article] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275327/ link to PMC article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12915604 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. [http://jco.ascopubs.org/content/23/1/133.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15625368 PubMed]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.23552/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18457330 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.23552/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18457330 PubMed]
 ==Low-dose (LD) IL-2 {{#subobject:a2e938|Regimen=1}}==
@@ Line 559: / Line 342: @@
 |-
 |[http://jco.ascopubs.org/content/21/16/3127.long Yang et al. 2003]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#High-dose_.28HD.29_IL-2|High-dose IL-2]]<br> Subcutaneous low-dose IL-2
 |-
@@ Line 581: / Line 359: @@
 |-
 |[http://jco.ascopubs.org/content/21/16/3127.long Yang et al. 2003]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#High-dose_.28HD.29_IL-2|High-dose IL-2]]<br> Intravenous low-dose IL-2
 |-
@@ Line 597: / Line 370: @@
 ===References===
-# 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. [http://jco.ascopubs.org/content/21/16/3127.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12915604 PubMed]
+# 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. [http://jco.ascopubs.org/content/21/16/3127.long link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275327/ link to PMC article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12915604 PubMed]
 ==Interferon alfa-2a (Roferon-A) {{#subobject:8f04d6|Regimen=1}}==
@@ Line 611: / Line 384: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa065044 Motzer et al. 2007]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#Sunitinib_.28Sutent.29|Sunitinib]]
 |-
@@ Line 634: / Line 402: @@
 |'''Comparator'''
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa066838 Hudes et al. 2007]
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa066838 Hudes et al. 2007 (ARCC)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |Interferon alfa-2a & Temsirolimus<br> [[Renal_cancer#Temsirolimus_.28Torisel.29|Temsirolimus]]
 |-
@@ Line 658: / Line 421: @@
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)61904-7/abstract Escudier et al. 2007 (AVOREN)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#Bevacizumab_.26_Interferon_alfa-2a|Bevacizumab & Interferon alfa-2a]]
 |-
 |[http://jco.ascopubs.org/content/26/33/5422.long Rini et al. 2008 (CALGB 90206)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#Bevacizumab_.26_Interferon_alfa-2a|Bevacizumab & Interferon alfa-2a]]
 |-
 |[http://jco.ascopubs.org/content/27/8/1280.long Escudier et al. 2009]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[Renal_cancer#Sorafenib_.28Nexavar.29|Sorafenib]]
 |-
@@ Line 700: / Line 448: @@
 ## '''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. [http://jco.ascopubs.org/content/28/13/2137.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20368558 PubMed]
 # 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. [http://jco.ascopubs.org/content/27/8/1280.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19171708 PubMed]
+==Pazopanib (Votrient) {{#subobject:443024|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Regimen {{#subobject:d6c07c|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|'''Comparator'''
+|Comparator [[Overall response rate|'''ORR''']]
+|-
+|[http://jco.ascopubs.org/content/28/3/475.long Hutson et al. 2010]
+|style="background-color:#eeee00"|Phase II
+|
+|
+|
+|-
+|[http://jco.ascopubs.org/content/28/6/1061.long Sternberg et al. 2010 (VEG105192)]
+|style="background-color:#00cd00"|Phase III
+|30% (95% CI 25-36%)
+|[[Renal_cancer#Placebo|Placebo]]
+|3% (95% CI 0-6%)
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 Motzer et al. 2013]
+|style="background-color:#00cd00"|Phase III
+|31% (95% CI 27-34%)
+|[[Renal_cancer#Sunitinib_.28Sutent.29|Sunitinib]]
+|25% (95% CI 21-28%)
+|-
+|}
+====Chemotherapy====
+*[[Pazopanib (Votrient)]] 800 mg PO once per day, given 1 hour before or 2 hours after meals
+**Dose may be decreased to 600 mg or 400 mg PO once per day depending on tolerability
+'''Given until progression of disease, unacceptable toxicity, death, or withdrawal of consent'''
+===References===
+# 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. [http://jco.ascopubs.org/content/28/3/475.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20008644 PubMed]
+# 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. [http://jco.ascopubs.org/content/28/6/1061.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20100962 PubMed]
+## '''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. [http://www.sciencedirect.com/science/article/pii/S095980491200980X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23321547 PubMed]
+# Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. [http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23964934 PubMed]
+## '''Update:''' Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014 May 1;370(18):1769-70. [http://www.nejm.org/doi/full/10.1056/NEJMc1400731 link to letter] [http://www.ncbi.nlm.nih.gov/pubmed/24785224 PubMed]
+==Placebo==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Regimen===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|-
+|[http://jco.ascopubs.org/content/28/6/1061.long Sternberg et al. 2010 (VEG105192)]
+|style="background-color:#00cd00"|Phase III
+|[[Renal_cancer#Pazopanib_.28Votrient.29|Pazopanib]]
+|-
+|}
+''No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.''
+===References===
+# 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. [http://jco.ascopubs.org/content/28/6/1061.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20100962 PubMed]
+## '''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. [http://www.ejcancer.com/article/S0959-8049(12)00980-X/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23321547 PubMed]
+==Regorafenib (Stivarga) {{#subobject:183793|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Regimen {{#subobject:a55057|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|-
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70364-9/fulltext Eisen et al. 2012]
+|style="background-color:#eeee00"|Phase II
+|40% (90% CI 28-53%)
+|-
+|}
+====Chemotherapy====
+*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21, given while fasting or after a light meal
+'''28-day cycles, given until progression of disease or unacceptable toxicity'''
+===References===
+# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70364-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22959186 PubMed]
+==Sorafenib (Nexavar) {{#subobject:fe45b0|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Regimen {{#subobject:b76687|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|'''Comparator'''
+|Comparator [[Overall response rate|'''ORR''']]
+|-
+|[http://jco.ascopubs.org/content/27/8/1280.long Escudier et al. 2009]
+|style="background-color:#00cd00"|Randomized Phase II
+|
+|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
+|
+|-
+|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.24864/abstract Stadler et al. 2010 (ARCCS)]
+|style="background-color:#eeee00"|Non-randomized
+|
+|
+|
+|-
+|[http://www.sciencedirect.com/science/article/pii/S1470204513704650 Hutson et al. 2013]
+|style="background-color:#00cd00"|Phase III
+|15%
+|[[Renal_cancer#Axitinib_.28Inlyta.29|Axitinib]]
+|32%
+|-
+|}
+====Chemotherapy====
+*[[Sorafenib (Nexavar)]] 400 mg PO BID
+**Can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity
+'''Continued until progression or intolerance'''
+===References===
+# 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. [http://jco.ascopubs.org/content/27/8/1280.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19171708 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.24864/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20082451 PubMed]
+# Hutson TE, Lesovoy V, Al-Shukri S, Stus VP, Lipatov ON, Bair AH, Rosbrook B, Chen C, Kim S, Vogelzang NJ. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1287-94. Epub 2013 Oct 25. [http://www.sciencedirect.com/science/article/pii/S1470204513704650 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24206640 PubMed]
+==Sunitinib (Sutent) {{#subobject:b4a97a|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Regimen {{#subobject:92e618|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|'''Comparator'''
+|Comparator [[Overall response rate|'''ORR''']]
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa065044 Motzer et al. 2007]
+|style="background-color:#00cd00"|Phase III
+|31%
+|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
+|6%
+|-
+|[http://jco.ascopubs.org/content/26/1/127.long Choueiri et al. 2008]
+|style="background-color:#eeee00"|Non-randomized
+|10%
+|
+|
+|-
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970162-7/fulltext Gore et al. 2009]
+|style="background-color:#eeee00"|Non-randomized
+|17%
+|
+|
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 Motzer et al. 2013]
+|style="background-color:#00cd00"|Phase III
+|25% (95% CI 21-28%)
+|[[Renal_cancer#Pazopanib_.28Votrient.29|Pazopanib]]
+|31% (95% CI 27-34%)
+|-
+|[http://jco.ascopubs.org/content/32/25/2765.long Motzer et al. 2014 (RECORD-3)]
+|style="background-color:#00cd00"|Randomized Phase II
+|
+|[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
+|
+|-
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00515-X/abstract Armstrong et al. 2016 (ASPEN)]
+|style="background-color:#00cd00"|Randomized Phase II
+|
+|[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
+|
+|-
+|}
+====Chemotherapy====
+*[[Sunitinib (Sutent)]] 50 mg PO once per day on days 1 to 28
+**Dose may be decreased to [[Sunitinib (Sutent)]] 37.5 mg or 25 mg PO once per day depending on tolerability
+'''42-day cycles, given until progression of disease or unacceptable toxicity'''
+===References===
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa065044 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17215529 PubMed]
+## '''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. [http://jco.ascopubs.org/content/27/22/3584.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19487381 PubMed]
+# Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, Zhou M, Rini BI, Bukowski RM, Escudier B. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol. 2008 Jan 1;26(1):127-31. [http://jco.ascopubs.org/content/26/1/127.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18165647 PubMed]
+# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970162-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19615940 PubMed]
+# Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. [http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23964934 PubMed]
+## '''Update:''' Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014 May 1;370(18):1769-70. [http://www.nejm.org/doi/full/10.1056/NEJMc1400731 link to letter] [http://www.ncbi.nlm.nih.gov/pubmed/24785224 PubMed]
+<!-- # '''Abstract:''' Robert John Motzer, Carlos H. Barrios, Tae Min Kim, Silvia Falcon, Thomas Cosgriff, W. Graydon Harker, Kenneth B. Pittman, Roberto Sabbatini, Sun Young Rha, Thomas W. Flaig, Ray D. Page, Sevil E. Bavbek, J. Thaddeus Beck, Poulam M Patel, Edward Schiff, Alexandra Vaury, Julie Niolat, Sven Gogov, Ozlem Anak, Jennifer Knox. Record-3: Phase II randomized trial comparing sequential first-line everolimus (EVE) and second-line sunitinib (SUN) versus first-line SUN and second-line EVE in patients with metastatic renal cell carcinoma (mRCC). 2013 ASCO Annual Meeting abstract 4504. [http://meetinglibrary.asco.org/content/113103-132 link to abstract] -->
+# 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. [http://jco.ascopubs.org/content/32/25/2765.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/25049330 PubMed]
+# Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, Lusk CM, Oberg S, George DJ. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016 Mar;17(3):378-88. Epub 2016 Jan 13. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00515-X/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26794930 PubMed]
+==Temsirolimus (Torisel) {{#subobject:8160ec|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Regimen {{#subobject:f56815|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|'''Comparator'''
+|Comparator [[Overall response rate|'''ORR''']]
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa066838 Hudes et al. 2007]
+|style="background-color:#00cd00"|Phase III
+|9% (95% CI 5-12%)
+|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]<br> Interferon alfa-2a & Temsirolimus
+|5% (95% CI 2-8%)<br>8% (95% CI 4-12%)
+|-
+|}
+====Chemotherapy====
+*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per week
+====Supportive medications====
+*[[Diphenhydramine (Benadryl)]] or similar H1 blocker 25 to 50 mg IV once 30 minutes prior to temsirolimus
+===References===
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa066838 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17538086 PubMed]
+=Metastatic disease, second-line=
+==Axitinib (Inlyta) {{#subobject:832684|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Regimen {{#subobject:a48a96|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|'''Comparator'''
+|Comparator [[Overall response rate|'''ORR''']]
+|-
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961613-9/fulltext Rini et al. 2011 (AXIS)]
+|style="background-color:#00cd00"|Phase III
+|19% (95% CI 15-24%)
+|[[Renal_cancer#Sorafenib_.28Nexavar.29_2|Sorafenib]]
+|9% (95% CI 7-13%)
+|-
+|}
+====Chemotherapy====
+*[[Axitinib (Inlyta)]] as follows:
+**5 mg PO BID for at least 2 weeks
+**Then if tolerated and BP not greater than 150/90, increased to 7 mg PO BID
+**Then if tolerated and BP not greater than 150/90, increased to 10 mg PO BID
+**Dose can be reduced to 2 to 3 mg PO BID if needed based on tolerability
+===References===
+# Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961613-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22056247 PubMed]
+## '''Update:''' Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552-62. Epub 2013 Apr 15. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70093-7/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23598172 PubMed]
+==Cabozantinib (Cabometyx) {{#subobject:pyr1|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Regimen {{#subobject:pyv1|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|'''Comparator'''
+|Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa1510016 Choueiri et al. 2015 (METEOR)]
+|style="background-color:#00cd00"|Phase III
+|21% (95% CI 16-28%)
+|[[#Everolimus_.28Afinitor.29_2|Everolimus]]
+|5% (95% CI 2-9%)
+|style="background-color:#00cd00"|Improved PFS
+|-
+|}
+''Patients had progressed after [[:Category:VEGF_inhibitors|VEGFR TKI]] treatment.''
+====Chemotherapy====
+*[[Cabozantinib (Cabometyx)]] 60 mg PO once per day
+**At least 2 hours before or 1 hour after meals according to the [https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf Cabozantinib (Cabometyx) package insert]
+'''Used as long as clinical benefit was perceived or unacceptable toxicity'''
+===References===
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1510016 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26406150 PubMed]
+## '''Update:''' ASCO 2016 Abstract 4506
+==Everolimus (Afinitor) {{#subobject:893557|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Regimen {{#subobject:9d436d|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|'''Comparator'''
+|Comparator [[Overall response rate|'''ORR''']]
+|-
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961039-9/fulltext Motzer et al. 2008 (RECORD-1)]
+|style="background-color:#00cd00"|Phase III
+|1%
+|[[Renal_cancer#Placebo|Placebo]]
+|0%
+|-
+|[http://jco.ascopubs.org/content/32/25/2765.long Motzer et al. 2014 (RECORD-3)]
+|style="background-color:#00cd00"|Randomized Phase II
+|
+|[[Renal_cancer#Sunitinib_.28Sutent.29_2|Sunitinib]]
+|
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa1510665 Motzer et al. 2015 (CheckMate 025)]
+|style="background-color:#00cd00"|Phase III
+|5%
+|[[Renal_cancer#Nivolumab_.28Opdivo.29|Nivolumab]]
+|25%
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa1510016 Choueiri et al. 2015 (METEOR)]
+|style="background-color:#00cd00"|Phase III
+|5% (95% CI 2-9%)
+|[[#Cabozantinib_.28Cabometyx.29|Cabozantinib]]
+|21% (95% CI 16-28%)
+|-
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext Motzer et al. 2015]
+|style="background-color:#00cd00"|Randomized Phase II
+|
+|[[#Everolimus_.26_Lenvatinib | Everolimus & Lenvatinib]]<br>[[#Lenvatinib_.28Lenvima.29|Lenvatinib]]
+|
+|-
+|}
+''Patients in '''RECORD-1''' and '''METEOR''' had progressed after [[:Category:VEGF_inhibitors|VEGFR TKI]] treatment. Patients in '''RECORD-3''' were pre-assigned to receive [[#Sunitinib_.28Sutent.29|sunitinib]] in the first-line. 72% of patients in '''Checkmate 025''' had anti-angiogenic therapy prior to progression.''
+====Chemotherapy====
+*[[Everolimus (Afinitor)]] 10 mg PO once per day
+**Dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability
+'''Given until progression of disease or unacceptable toxicity.'''
+===References===
+# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961039-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18653228 PubMed]
+## '''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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25219/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20549832 PubMed]
+<!-- # '''Abstract:''' Robert John Motzer, Carlos H. Barrios, Tae Min Kim, Silvia Falcon, Thomas Cosgriff, W. Graydon Harker, Kenneth B. Pittman, Roberto Sabbatini, Sun Young Rha, Thomas W. Flaig, Ray D. Page, Sevil E. Bavbek, J. Thaddeus Beck, Poulam M Patel, Edward Schiff, Alexandra Vaury, Julie Niolat, Sven Gogov, Ozlem Anak, Jennifer Knox. Record-3: Phase II randomized trial comparing sequential first-line everolimus (EVE) and second-line sunitinib (SUN) versus first-line SUN and second-line EVE in patients with metastatic renal cell carcinoma (mRCC). 2013 ASCO Annual Meeting abstract 4504. [http://meetinglibrary.asco.org/content/113103-132 link to abstract] -->
+# 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. [http://jco.ascopubs.org/content/32/25/2765.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/25049330 PubMed]
+# 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 Sep 25. [http://www.nejm.org/doi/full/10.1056/NEJMoa1510665 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26406148 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1510016 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26406150 PubMed]
+## '''Update:''' ASCO 2016 Abstract 4506
+# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26482279 PubMed]
+## '''Update:''' Motzer RJ, Hutson TE, Ren M3, Dutcus C3, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00543-4/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26758760 PubMed]
+==Everolimus & Lenvatinib {{#subobject:21039d|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Regimen {{#subobject:71ef67|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|'''Comparator'''
+|Comparator [[Overall response rate|'''ORR''']]
+|-
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/abstract Motzer et al. 2015]
+|style="background-color:#00cd00"|Randomized Phase II
+|43% (95% CI 29-58%)
+|[[#Everolimus_.28Afinitor.29|Everolimus]]<br> [[#Lenvatinib_.28Lenvima.29|Lenvatinib]]
+|6% (95% CI 1-17%)<br>27% (95% CI 16-41%)
+|-
+|}
+''Patients had progressed after [[:Category:VEGF_inhibitors|VEGFR TKI]] treatment.''
+====Chemotherapy====
+*[[Everolimus (Afinitor)]] 5 mg PO once per day
+*[[Lenvatinib (Lenvima)]] 18 mg PO once per day
+'''Continued until progression or unacceptable toxicity'''
+===References===
+# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26482279 PubMed]
+## '''Update:''' Motzer RJ, Hutson TE, Ren M3, Dutcus C3, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00543-4/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26758760 PubMed]
 ==Lenvatinib (Lenvima) {{#subobject:PYR3|Regimen=1}}==
@@ Line 713: / Line 852: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/abstract Motzer et al. 2015]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[#Everolimus_.28Afinitor.29|Everolimus]]<br>[[#Everolimus_.26_Lenvatinib | Everolimus & Lenvatinib]]
 |-
 |}
-''The 5/13/2016 FDA approved use of Lenvatinib (Lenvima) is in combination with [[Everolimus (Afinitor)]]. In Motzer et al. 2015, "single-agent lenvatinib significantly prolonged progression-free survival compared with everolimus alone.  Everolimus & levatinib had a non-statistically signficant improved PFS compared to single-agent levatinib.''
+''Note: The 5/13/2016 FDA approved use of Lenvatinib (Lenvima) is in combination with [[Everolimus (Afinitor)]]. In Motzer et al. 2015, "single-agent lenvatinib significantly prolonged progression-free survival compared with everolimus alone. Everolimus & levatinib had a non-statistically signficant improved PFS compared to single-agent levatinib.''
 ====Chemotherapy====
 *[[Lenvatinib (Lenvima)]] 24 mg PO once per day
@@ Line 744: / Line 878: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
-|Pt Population
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1510665 Motzer et al. 2015 (CheckMate 025)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |25%
-|[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
+|[[#Everolimus_.28Afinitor.29_2|Everolimus]]
 |5%
-|Mixed pop; 72% had anti-angiogenic therapy
 |-
 |}
@@ Line 779: / Line 906: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
-|Pt Population
 |-
 |[http://jco.ascopubs.org/content/28/3/475.long Hutson et al. 2010]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-|
 |
 |
@@ Line 794: / Line 914: @@
 |-
 |[http://jco.ascopubs.org/content/28/6/1061.long Sternberg et al. 2010 (VEG105192)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |30% (95% CI 25-36%)
-|[[Renal_cancer#Placebo|Placebo]]
+|[[#Placebo_2|Placebo]]
 |3% (95% CI 0-6%)
-|Treatment-naive and cytokine-pretreated
 |-
 |[http://www.clinical-genitourinary-cancer.com/article/S1558-7673(13)00052-9/abstract Hainsworth et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-|
 |
 |
 |
-|-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 Motzer et al. 2013]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|31% (95% CI 27-34%)
-|[[Renal_cancer#Sunitinib_.28Sutent.29|Sunitinib]]
-|25% (95% CI 21-28%)
-|Treatment naive
 |-
 |}
@@ Line 841: / Line 937: @@
 ## '''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. [http://www.sciencedirect.com/science/article/pii/S095980491200980X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://www.clinical-genitourinary-cancer.com/article/S1558-7673(13)00052-9/abstract link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23665131 PubMed]
-# Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. [http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23964934 PubMed]
-## '''Update:''' Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014 May 1;370(18):1769-70. [http://www.nejm.org/doi/full/10.1056/NEJMc1400731 link to letter] [http://www.ncbi.nlm.nih.gov/pubmed/24785224 PubMed]
-==Placebo {{#subobject:542c1a|Regimen=1}}==
+==Placebo==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 850: / Line 944: @@
 |}
-===Regimen {{#subobject:48f65e|Variant=1}}===
+===Regimen===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 857: / Line 951: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa060655 Escudier et al. 2007 (TARGET)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#Sorafenib_.28Nexavar.29|Sorafenib]]
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961039-9/fulltext Motzer et al. 2008 (RECORD-1)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
 |-
 |[http://jco.ascopubs.org/content/28/6/1061.long Sternberg et al. 2010 (VEG105192)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Renal_cancer#Pazopanib_.28Votrient.29|Pazopanib]]
 |-
@@ Line 895: / Line 974: @@
 ## '''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. [http://www.ejcancer.com/article/S0959-8049(12)00980-X/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23321547 PubMed]
-==Regorafenib (Stivarga) {{#subobject:183793|Regimen=1}}==
+==Sorafenib (Nexavar) {{#subobject:6e18d8|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#toc|back to top]]
 |}
-===Regimen {{#subobject:a55057|Variant=1}}===
+===Regimen {{#subobject:a50d71|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|[[Overall response rate|'''ORR''']]
-|-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70364-9/fulltext Eisen et al. 2012]
-|<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-|40% (90% CI 28-53%)
-|-
-|}
-====Chemotherapy====
-*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21, given while fasting or after a light meal
-'''28-day cycles, given until progression of disease or unacceptable toxicity'''
-===References===
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70364-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22959186 PubMed]
-==Sorafenib (Nexavar) {{#subobject:fe45b0|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
-===Regimen {{#subobject:b76687|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 936: / Line 986: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
-|Pt Population
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa060655 Escudier et al. 2007 (TARGET)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |10%
 |[[Renal_cancer#Placebo|Placebo]]
 |2%
-|Treated with cytokines previously
-|-
-|[http://jco.ascopubs.org/content/27/8/1280.long Escudier et al. 2009]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
-|
-|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
-|
-|
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1002/cncr.24864/abstract Stadler et al. 2010 (ARCCS)]
-|<span
+|style="background-color:#eeee00"|Non-randomized
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
-|
 |
 |
@@ Line 975: / Line 1,000: @@
 |-
 |[http://annonc.oxfordjournals.org/content/22/8/1812.long Beck et al. 2011 (EU-ARCCS)]
-|<span
+|style="background-color:#eeee00"|Non-randomized
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
-|
 |
 |
@@ Line 987: / Line 1,006: @@
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961613-9/fulltext Rini et al. 2011 (AXIS)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |9% (95% CI 7-13%)
 |[[Renal_cancer#Axitinib_.28Inlyta.29|Axitinib]]
 |19% (95% CI 15-24%)
-|Treatment exposed (sunitinib, cytokines)
-|-
-|[http://www.sciencedirect.com/science/article/pii/S1470204513704650 Hutson et al. 2013]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|15%
-|[[Renal_cancer#Axitinib_.28Inlyta.29|Axitinib]]
-|32%
-|Treatment naive
 |-
 |}
@@ Line 1,025: / Line 1,026: @@
 # Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961613-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22056247 PubMed]
 ## '''Update:''' Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552-62. Epub 2013 Apr 15. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70093-7/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23598172 PubMed]
-# Hutson TE, Lesovoy V, Al-Shukri S, Stus VP, Lipatov ON, Bair AH, Rosbrook B, Chen C, Kim S, Vogelzang NJ. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1287-94. Epub 2013 Oct 25. [http://www.sciencedirect.com/science/article/pii/S1470204513704650 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24206640 PubMed]
-==Sunitinib (Sutent) {{#subobject:b4a97a|Regimen=1}}==
+==Sunitinib (Sutent) {{#subobject:f929da|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#toc|back to top]]
 |}
-===Regimen {{#subobject:92e618|Variant=1}}===
+===Regimen {{#subobject:955949|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,039: / Line 1,039: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
-|Pt Population
-|-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa065044 Motzer et al. 2007]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|31%
-|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
-|6%
-|Treatment naive
-|-
-|[http://jco.ascopubs.org/content/26/1/127.long Choueiri et al. 2008]
-|<span
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
-|10%
-|
-|
-|
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970162-7/fulltext Gore et al. 2009]
-|<span
+|style="background-color:#eeee00"|Non-randomized
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |17%
-|
 |
 |
-|-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 Motzer et al. 2013]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|25% (95% CI 21-28%)
-|[[Renal_cancer#Pazopanib_.28Votrient.29|Pazopanib]]
-|31% (95% CI 27-34%)
-|Treatment naive
 |-
 |[http://jco.ascopubs.org/content/32/25/2765.long Motzer et al. 2014 (RECORD-3)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |
 |[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
-|
 |
 |-
@@ Line 1,109: / Line 1,060: @@
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa065044 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17215529 PubMed]
-## '''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. [http://jco.ascopubs.org/content/27/22/3584.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19487381 PubMed]
-# Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, Zhou M, Rini BI, Bukowski RM, Escudier B. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol. 2008 Jan 1;26(1):127-31. [http://jco.ascopubs.org/content/26/1/127.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18165647 PubMed]
 # 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970162-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19615940 PubMed]
 <!-- # '''Abstract:''' Robert John Motzer, Carlos H. Barrios, Tae Min Kim, Silvia Falcon, Thomas Cosgriff, W. Graydon Harker, Kenneth B. Pittman, Roberto Sabbatini, Sun Young Rha, Thomas W. Flaig, Ray D. Page, Sevil E. Bavbek, J. Thaddeus Beck, Poulam M Patel, Edward Schiff, Alexandra Vaury, Julie Niolat, Sven Gogov, Ozlem Anak, Jennifer Knox. Record-3: Phase II randomized trial comparing sequential first-line everolimus (EVE) and second-line sunitinib (SUN) versus first-line SUN and second-line EVE in patients with metastatic renal cell carcinoma (mRCC). 2013 ASCO Annual Meeting abstract 4504. [http://meetinglibrary.asco.org/content/113103-132 link to abstract] -->
 # 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. [http://jco.ascopubs.org/content/32/25/2765.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/25049330 PubMed]
-# Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. [http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23964934 PubMed]
-## '''Update:''' Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014 May 1;370(18):1769-70. [http://www.nejm.org/doi/full/10.1056/NEJMc1400731 link to letter] [http://www.ncbi.nlm.nih.gov/pubmed/24785224 PubMed]
-==Temsirolimus (Torisel) {{#subobject:8160ec|Regimen=1}}==
+=Metastatic disease, third-line=
+==Sorafenib (Nexavar) {{#subobject:7b51ba|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#toc|back to top]]
 |}
-===Regimen {{#subobject:f56815|Variant=1}}===
+===Regimen {{#subobject:87cb7d|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|[[Overall response rate|'''ORR''']]
 |'''Comparator'''
-|Comparator [[Overall response rate|'''ORR''']]
-|Pt Population
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa066838 Hudes et al. 2007]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70030-0/abstract Motzer et al. 2014]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Dovitinib (TKI-258)]]
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|9% (95% CI 5-12%)
-|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]<br> Interferon alfa-2a & Temsirolimus
-|5% (95% CI 2-8%)<br>8% (95% CI 4-12%)
-|Treatment naive
 |-
 |}
 ====Chemotherapy====
-*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per week
+*[[Sorafenib (Nexavar)]] 400 mg PO BID
-====Supportive medications====
-*[[Diphenhydramine (Benadryl)]] or similar H1 blocker 25 to 50 mg IV once 30 minutes prior to temsirolimus
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa066838 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17538086 PubMed]
+# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70030-0/abstract link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24556040 PubMed]
 [[Category:Chemotherapy regimens]]
 [[Category:Solid oncology regimens]]
 [[Category:Genitourinary (GU) oncology regimens]]

Difference between revisions of "Renal cell carcinoma"

Revision as of 18:34, 15 September 2016

Metastatic disease, first-line

Axitinib (Inlyta)

Regimen

Chemotherapy

References

Bevacizumab (Avastin)

Regimen

Chemotherapy

References

Bevacizumab & Erlotinib

Regimen

Chemotherapy

References

Bevacizumab & Interferon alfa-2a

Regimen

Chemoimmunotherapy

References

Erlotinib (Tarceva)

Regimen

Chemotherapy

References

Everolimus (Afinitor)

Regimen

Chemotherapy

References

Gemcitabine & Doxorubicin

Regimen

Chemotherapy

Supportive medications

References

Gemcitabine & Sunitinib

Regimen #1

Chemotherapy

Regimen #2

Chemotherapy

References

High-dose (HD) IL-2

Example orders

Regimen #1

Immunotherapy

Supportive medications

Regimen #2

Immunotherapy

Regimen #3

Immunotherapy

Supportive medications

References

Low-dose (LD) IL-2

Regimen #1, Intravenous

Immunotherapy

Regimen #2, Subcutaneous

Immunotherapy

References

Interferon alfa-2a (Roferon-A)

Regimen #1

Immunotherapy

Regimen #2

Immunotherapy

Regimen #3

Immunotherapy

References

Pazopanib (Votrient)

Regimen

Chemotherapy

References

Placebo

Regimen

References

Regorafenib (Stivarga)

Regimen

Chemotherapy

References

Sorafenib (Nexavar)

Regimen

Chemotherapy

References

Sunitinib (Sutent)

Regimen