Difference between revisions of "Renal cell carcinoma"

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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|19% (95% CI 15 - 24)  
+
|19% (95% CI 15-24%)  
 
|[[Renal_cancer#Sorafenib_.28Nexavar.29|Sorafenib]]
 
|[[Renal_cancer#Sorafenib_.28Nexavar.29|Sorafenib]]
−
|9% (95% CI 7 - 13)
+
|9% (95% CI 7-13%)
 
|Treatment exposed (sunitinib, cytokines)
 
|Treatment exposed (sunitinib, cytokines)
 
|-
 
|-
Line 45: Line 45:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|32% (95% CI NR)
+
|32%
 
|[[Renal_cancer#Sorafenib_.28Nexavar.29|Sorafenib]]
 
|[[Renal_cancer#Sorafenib_.28Nexavar.29|Sorafenib]]
−
|15% (95% CI NR)
+
|15%
 
|Treatment naive
 
|Treatment naive
 
|-
 
|-
 
|}
 
|}
−
*[[Axitinib (Inlyta)]] 5 mg PO BID x at least 2 weeks
+
====Chemotherapy====
 +
*[[Axitinib (Inlyta)]] 5 mg PO BID for at least 2 weeks
 
**Then if tolerated and BP not greater than 150/90, increased to [[Axitinib (Inlyta)]] 7 mg PO BID
 
**Then if tolerated and BP not greater than 150/90, increased to [[Axitinib (Inlyta)]] 7 mg PO BID
 
***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 [[Axitinib (Inlyta)]] 10 mg PO BID
Line 82: Line 83:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Randomized Phase II</span>
 
border-style:solid;">Randomized Phase II</span>
−
|13% (95% CI NR)
+
|13%
 
|[[Renal_cancer#Bevacizumab_.26_Erlotinib|Bevacizumab & Erlotinib]]
 
|[[Renal_cancer#Bevacizumab_.26_Erlotinib|Bevacizumab & Erlotinib]]
−
|14% (95% CI NR)
+
|14%
 
|Treatment naive
 
|Treatment naive
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV over 90 minutes once every 2 weeks
 
*[[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
 
**Can subsequently be reduced to 60 and 30 minute infusions as tolerated
Line 117: Line 119:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV over 90 minutes once every 2 weeks
 
*[[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  
 
**Can subsequently be reduced to 60 and 30 minute infusions as tolerated  
Line 146: Line 148:
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 
|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
 
|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
−
|-
 
−
!colspan="4" align="center"|
 
 
|-
 
|-
 
|[http://jco.ascopubs.org/content/26/33/5422.long Rini et al. 2008 (CALGB 90206)]
 
|[http://jco.ascopubs.org/content/26/33/5422.long Rini et al. 2008 (CALGB 90206)]
Line 159: Line 159:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemoimmunotherapy====
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once every 2 weeks
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once every 2 weeks
 
*[[Interferon alfa-2a (Roferon-A)]] 9 million units SC 3 times per week  
 
*[[Interferon alfa-2a (Roferon-A)]] 9 million units SC 3 times per week  
Line 194: Line 194:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|21% (95% CI 16 - 28)  
+
|21% (95% CI 16-28%)  
 
|[[#Everolimus_.28Afinitor.29|Everolimus]]
 
|[[#Everolimus_.28Afinitor.29|Everolimus]]
−
|5% (95% CI 2- 9)
+
|5% (95% CI 2-9%)
 
|Progressed after VEGFR TKI tx
 
|Progressed after VEGFR TKI tx
 
|<span
 
|<span
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|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 
*[[Cabozantinib (Cabometyx)]] 60 mg PO once per day
 
*[[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]
 
**At least 2 hours before or 1 hour after meals according to the [https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf Cabozantinib (Cabometyx) package insert]
Line 233: Line 234:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
−
|11% (95% CI 3 - 24)
+
|11% (95% CI 3-24%)
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Erlotinib (Tarceva)]] 150 mg PO once per day, given 1 hour before or 2 hours after meals
 
*[[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===
 
===References===
Line 265: Line 266:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|1% (95% CI NR)
+
|1%
 
|[[Renal_cancer#Placebo|Placebo]]
 
|[[Renal_cancer#Placebo|Placebo]]
−
|0% (95% CI NR)
+
|0%
 
|Progessed after VEGFR TKI tx
 
|Progessed after VEGFR TKI tx
 
|-
 
|-
Line 279: Line 280:
 
|
 
|
 
|[[Renal_cancer#Sunitinib_.28Sutent.29|Sunitinib]]
 
|[[Renal_cancer#Sunitinib_.28Sutent.29|Sunitinib]]
 +
|
 +
|
 
|-
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1510665 Motzer et al. 2015 (CheckMate 025)]
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1510665 Motzer et al. 2015 (CheckMate 025)]
Line 287: Line 290:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|5% (95% CI NR)
+
|5%
 
|[[Renal_cancer#Nivolumab_.28Opdivo.29|Nivolumab]]
 
|[[Renal_cancer#Nivolumab_.28Opdivo.29|Nivolumab]]
−
|25% (95% CI n/a)
+
|25%
 
|Mixed pop; 72% had anti-angiogenic therapy
 
|Mixed pop; 72% had anti-angiogenic therapy
 
|-
 
|-
Line 299: Line 302:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|5% (95% CI 2- 9)
+
|5% (95% CI 2-9%)
 
|[[#Cabozantinib_.28Cabometyx.29|Cabozantinib]]
 
|[[#Cabozantinib_.28Cabometyx.29|Cabozantinib]]
−
|21% (95% CI 16 - 28)
+
|21% (95% CI 16-28%)
 
|Progressed after VEGFR TKI tx
 
|Progressed after VEGFR TKI tx
 
|-
 
|-
Line 313: Line 316:
 
|
 
|
 
|[[#Everolimus_.26_Lenvatinib | Everolimus & Lenvatinib]]<br>[[#Lenvatinib_.28Lenvima.29|Lenvatinib]]
 
|[[#Everolimus_.26_Lenvatinib | Everolimus & Lenvatinib]]<br>[[#Lenvatinib_.28Lenvima.29|Lenvatinib]]
 +
|
 +
|
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day
 
*[[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
 
**Dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability
Line 352: Line 358:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Randomized Phase II</span>
 
border-style:solid;">Randomized Phase II</span>
−
|43% (95% CI 29 - 58)
+
|43% (95% CI 29-58%)
 
|[[#Everolimus_.28Afinitor.29|Everolimus]]<br> [[#Lenvatinib_.28Lenvima.29|Lenvatinib]]
 
|[[#Everolimus_.28Afinitor.29|Everolimus]]<br> [[#Lenvatinib_.28Lenvima.29|Lenvatinib]]
−
|6% (95% CI 1-17)<br>27% (95% CI 16 - 41)
+
|6% (95% CI 1-17%)<br>27% (95% CI 16-41%)
 
|progressed after VEGFR TKI tx
 
|progressed after VEGFR TKI tx
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 
*[[Everolimus (Afinitor)]] 5 mg PO once per day
 
*[[Everolimus (Afinitor)]] 5 mg PO once per day
 
*[[Lenvatinib (Lenvima)]] 18 mg PO once per day
 
*[[Lenvatinib (Lenvima)]] 18 mg PO once per day
Line 372: Line 379:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
===Regimen, Roubaud et al. 2011 & Haas et al. 2012 (ECOG 8802) {{#subobject:bdc472|Variant=1}}===
+
===Regimen {{#subobject:bdc472|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.springerlink.com/content/dnk52234n2567m5h/?MUD=MP Haas et al. 2012 (ECOG 8802)]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 380: Line 391:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1500 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 +
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV push once on day 1
  
−
*[[Gemcitabine (Gemzar)]] 1500 mg/m2 IV over 30 minutes once on day 1
+
'''14-day cycles, given until cumulative doxorubicin dose of 300 to 450 mg/m<sup>2</sup> (depending on cardiac function), progression of disease, or unacceptable toxicity'''
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV push once on day 1
 
  
−
'''14-day cycles, given until cumulative Doxorubicin (Adriamycin) dose of 300 to 450 mg/m2 (depending on cardiac function), progression of disease, or unacceptable toxicity'''
+
====Supportive medications====
−
 
 
−
Supportive medications:
 
 
*One of the following:
 
*One of the following:
 
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on starting on day 2 or 3, given until day 10
 
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on starting on day 2 or 3, given until day 10
Line 392: Line 405:
  
 
===References===
 
===References===
−
# Roubaud G, Gross-Goupil M, Wallerand H, de Clermont H, Dilhuydy MS, Ravaud A. Combination of gemcitabine and doxorubicin in rapidly progressive metastatic renal cell carcinoma and/or sarcomatoid renal cell carcinoma. Oncology. 2011;80(3-4):214-8. Epub 2011 Jul 1. [http://content.karger.com/produktedb/produkte.asp?DOI=10.1159/000329078 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21720184 PubMed]
 
 
# 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. [http://www.springerlink.com/content/dnk52234n2567m5h/?MUD=MP link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21298497 PubMed]
 
# 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. [http://www.springerlink.com/content/dnk52234n2567m5h/?MUD=MP link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21298497 PubMed]
  
Line 400: Line 412:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
===Regimen #1, Michaelson et al. 2013 {{#subobject:py1|Variant=1}}===
+
===Regimen #1 {{#subobject:py1|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span style="background:#EEEE00; padding:3px 6px 3px 6px; border-color:black; border-width:2px; border-style:solid;">Phase II</span>  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.29503/abstract Michaelson et al. 2015]
 +
|<span  
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
|-
 +
|}
  
−
''Patients in Michaelson et al. 2013 had disease with sarcomatoid features.''
+
''Patients had disease with sarcomatoid features.''
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
+
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
*[[Sunitinib (Sutent)]] 37.5 mg PO once per day on days 1 to 14
 
*[[Sunitinib (Sutent)]] 37.5 mg PO once per day on days 1 to 14
  
 
'''21-day cycles'''
 
'''21-day cycles'''
  
−
===Regimen #2, Pandya et al. 2011 {{#subobject:e9a6b9|Variant=1}}===
+
===Regimen #2 {{#subobject:e9a6b9|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2011.10096.x/full Pandya et al. 2011]
 +
|<span  
 
style="background:#ff0000;
 
style="background:#ff0000;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Retrospective</span>
 
border-style:solid;">Retrospective</span>
−
 
+
|-
−
*[[Gemcitabine (Gemzar)]] 750 mg/m2 IV over 90 minutes once per day on days 1 & 8
+
|}
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 750 mg/m<sup>2</sup> 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
 
*[[Sunitinib (Sutent)]] 37.5 mg PO once per day on days 2 to 15
  
Line 425: Line 455:
  
 
===References===
 
===References===
−
# 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. doi: 10.1111/j.1464-410X.2011.10096.x. Epub 2011 Feb 14. [http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2011.10096.x/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21320274 PubMed]
+
# '''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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2011.10096.x/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21320274 PubMed]
−
# '''Abstract:''' M Dror Michaelson, David F. McDermott, Michael B. Atkins, Daniel C. Cho, Kara M. Olivier, Abraham B. Schwarzberg, Toni K. Choueiri. Combination of antiangiogenic therapy and cytotoxic chemotherapy for sarcomatoid renal cell carcinoma. 2013 ASCO Annual Meeting abstract 4512. [http://meetinglibrary.asco.org/content/110415-132 link to abstract]
+
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.29503/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26058385 PubMed]
  
 
==High-dose (HD) IL-2 {{#subobject:d95f4e|Regimen=1}}==
 
==High-dose (HD) IL-2 {{#subobject:d95f4e|Regimen=1}}==
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|-
 
|-
 
|}
 
|}
 +
====Immunotherapy====
 +
*[[Aldesleukin (Proleukin)|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
  
−
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 600,000 units/kg IV every 8 hours x up to 14 doses per week, on days 1 to 5, 15 to 19
+
'''28-day cycle for up to 3 cycles'''
  
−
'''28-day cycle x up to 3 cycles'''
+
====Supportive medications====
−
 
 
−
Supportive medications:
 
 
*[[Ciprofloxacin (Cipro)]] 250 mg PO BID on days 1 to 10, 15 to 24
 
*[[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
 
*All antihypertensive therapy discontinued at least 24 hours before each cycle
Line 483: Line 513:
 
|-
 
|-
 
|}
 
|}
 +
====Immunotherapy====
 +
*[[Aldesleukin (Proleukin)|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, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours for up to 15 doses is given again
  
−
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 15 doses
+
'''8-week cycle for up to 2 cycles'''
−
**Then after 7 to 10 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 15 doses is given again
 
  
−
'''8-week cycle x up to 2 cycles'''
+
===Regimen #3 {{#subobject:9a662|Variant=1}}===
−
 
+
{| border="1" style="text-align:center;" !align="left"
−
===Regimen #3, Klapper et al. 2008 {{#subobject:9a662|Variant=1}}===
+
|'''Study'''
−
Level of Evidence:
+
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
−
<span  
+
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.23552/full Klapper et al. 2008]
 +
|<span  
 
style="background:#ff0000;
 
style="background:#ff0000;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 497: Line 531:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Retrospective</span>
 
border-style:solid;">Retrospective</span>
−
 
+
|-
−
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 12 doses (reduced from originally up to 15 doses due to few patients tolerating 15 doses)
+
|}
−
**Then after 10 to 15 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 12 doses is given again  
+
====Immunotherapy====
 +
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours for up to 12 doses (reduced from originally up to 15 doses due to few patients tolerating 15 doses)
 +
**Then after 10 to 15 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours for up to 12 doses is given again  
  
 
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)
 
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:
+
====Supportive medications====
 
*"Routine administration of antipyretics, anti-inflammatories, antiemetics, antidiarrheals, and H2 antagonists."
 
*"Routine administration of antipyretics, anti-inflammatories, antiemetics, antidiarrheals, and H2 antagonists."
  
Line 532: Line 568:
 
|-
 
|-
 
|}
 
|}
 +
====Immunotherapy====
 +
*[[Aldesleukin (Proleukin)|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, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 72,000 units/kg IV every 8 hours for up to 15 doses is given again
  
−
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 72,000 units/kg IV every 8 hours x up to 15 doses
+
'''8-week cycle for up to 2 cycles'''
−
**Then after 7 to 10 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 72,000 units/kg IV every 8 hours x up to 15 doses is given again
 
−
 
 
−
'''8-week cycle x up to 2 cycles'''
 
  
 
===Regimen #2, Subcutaneous {{#subobject:cbb5b2|Variant=1}}===
 
===Regimen #2, Subcutaneous {{#subobject:cbb5b2|Variant=1}}===
Line 554: Line 590:
 
|-
 
|-
 
|}
 
|}
 +
====Immunotherapy====
 +
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 250,000 units/kg SC once per day for 5 days on week 1
 +
**Then [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 125,000 units/kg SC once per day for 5 days per week during weeks 2 to 6
  
−
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 250,000 units/kg SC once per day x 5 days on week 1
+
'''8-week cycle for up to 2 cycles'''
−
**Then [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 125,000 units/kg SC once per day x 5 days per week during weeks 2 to 6
 
−
 
 
−
'''8-week cycle x up to 2 cycles'''
 
  
 
===References===
 
===References===
Line 584: Line 620:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Immunotherapy====
 
*[[Interferon alfa-2a (Roferon-A)]] as follows:
 
*[[Interferon alfa-2a (Roferon-A)]] as follows:
 
**Week 1: 3 million units SC 3 times per week
 
**Week 1: 3 million units SC 3 times per week
Line 608: Line 644:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Immunotherapy====
 
*[[Interferon alfa-2a (Roferon-A)]] as follows:
 
*[[Interferon alfa-2a (Roferon-A)]] as follows:
 
**Week 1: 3 million units SC 3 times per week
 
**Week 1: 3 million units SC 3 times per week
Line 629: Line 665:
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 
|[[Renal_cancer#Bevacizumab_.26_Interferon_alfa-2a|Bevacizumab & Interferon alfa-2a]]
 
|[[Renal_cancer#Bevacizumab_.26_Interferon_alfa-2a|Bevacizumab & Interferon alfa-2a]]
−
|-
 
−
!colspan="4" align="center"|
 
 
|-
 
|-
 
|[http://jco.ascopubs.org/content/26/33/5422.long Rini et al. 2008 (CALGB 90206)]
 
|[http://jco.ascopubs.org/content/26/33/5422.long Rini et al. 2008 (CALGB 90206)]
Line 640: Line 674:
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 
|[[Renal_cancer#Bevacizumab_.26_Interferon_alfa-2a|Bevacizumab & Interferon alfa-2a]]
 
|[[Renal_cancer#Bevacizumab_.26_Interferon_alfa-2a|Bevacizumab & Interferon alfa-2a]]
−
|-
 
−
!colspan="4" align="center"|
 
 
|-
 
|-
 
|[http://jco.ascopubs.org/content/27/8/1280.long Escudier et al. 2009]
 
|[http://jco.ascopubs.org/content/27/8/1280.long Escudier et al. 2009]
Line 653: Line 685:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Immunotherapy====
 
*[[Interferon alfa-2a (Roferon-A)]] 9 million units SC 3 times per week  
 
*[[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
 
**Dose can be reduced to 3 or 6 million units SC 3 times per week based on tolerability
Line 691: Line 723:
 
|}
 
|}
 
''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.''
 
''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
 
*[[Lenvatinib (Lenvima)]] 24 mg PO once per day
  
Line 720: Line 753:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|25% (95% CI n/a)
+
|25%
 
|[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
 
|[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
−
|5% (95% CI n/a)
+
|5%
 
|Mixed pop; 72% had anti-angiogenic therapy
 
|Mixed pop; 72% had anti-angiogenic therapy
 
|-
 
|-
 
|}
 
|}
 +
====Immunotherapy====
 
*[[Nivolumab (Opdivo)]] 3 mg/kg IV over 60 minutes on day 1
 
*[[Nivolumab (Opdivo)]] 3 mg/kg IV over 60 minutes on day 1
  
Line 754: Line 788:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|
 +
|
 +
|
 +
|
 
|-
 
|-
 
|[http://jco.ascopubs.org/content/28/6/1061.long Sternberg et al. 2010 (VEG105192)]
 
|[http://jco.ascopubs.org/content/28/6/1061.long Sternberg et al. 2010 (VEG105192)]
Line 762: Line 800:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|30% (95% CI 25 - 36)  
+
|30% (95% CI 25-36%)  
 
|[[Renal_cancer#Placebo|Placebo]]
 
|[[Renal_cancer#Placebo|Placebo]]
−
|3% (95% CI 0 - 6)
+
|3% (95% CI 0-6%)
 
|Treatment-naive and cytokine-pretreated
 
|Treatment-naive and cytokine-pretreated
 
|-
 
|-
Line 774: Line 812:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|
 +
|
 +
|
 +
|
 
|-
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 Motzer et al. 2013]
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 Motzer et al. 2013]
Line 782: Line 824:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|31% (95% CI 27 - 34)
+
|31% (95% CI 27-34%)
 
|[[Renal_cancer#Sunitinib_.28Sutent.29|Sunitinib]]
 
|[[Renal_cancer#Sunitinib_.28Sutent.29|Sunitinib]]
−
|25% (95% CI 21 - 28)
+
|25% (95% CI 21-28%)
 
|Treatment naive
 
|Treatment naive
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Pazopanib (Votrient)]] 800 mg PO once per day, given 1 hour before or 2 hours after meals
 
*[[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  
 
**Dose may be decreased to 600 mg or 400 mg PO once per day depending on tolerability  
Line 822: Line 864:
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 
|[[Renal_cancer#Sorafenib_.28Nexavar.29|Sorafenib]]
 
|[[Renal_cancer#Sorafenib_.28Nexavar.29|Sorafenib]]
−
|-
 
−
!colspan="4" align="center"|
 
 
|-
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961039-9/fulltext Motzer et al. 2008 (RECORD-1)]
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961039-9/fulltext Motzer et al. 2008 (RECORD-1)]
Line 833: Line 873:
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 
|[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
 
|[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
−
|-
 
−
!colspan="4" align="center"|
 
 
|-
 
|-
 
|[http://jco.ascopubs.org/content/28/6/1061.long Sternberg et al. 2010 (VEG105192)]
 
|[http://jco.ascopubs.org/content/28/6/1061.long Sternberg et al. 2010 (VEG105192)]
Line 875: Line 913:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
−
|39.6% (90% CI 27.7 - 52.5)
+
|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
 
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21, given while fasting or after a light meal
  
Line 907: Line 945:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|10% (95% CI NR)
+
|10%
 
|[[Renal_cancer#Placebo|Placebo]]
 
|[[Renal_cancer#Placebo|Placebo]]
−
|2% (95% CI NR)
+
|2%
 
|Treated with cytokines previously
 
|Treated with cytokines previously
 
|-
 
|-
Line 919: Line 957:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Randomized Phase II</span>
 
border-style:solid;">Randomized Phase II</span>
 +
|
 
|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
 
|[[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)]
 
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.24864/abstract Stadler et al. 2010 (ARCCS)]
Line 928: Line 969:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Non-randomized</span>
 
border-style:solid;">Non-randomized</span>
 +
|
 +
|
 +
|
 +
|
 
|-
 
|-
 
|[http://annonc.oxfordjournals.org/content/22/8/1812.long Beck et al. 2011 (EU-ARCCS)]
 
|[http://annonc.oxfordjournals.org/content/22/8/1812.long Beck et al. 2011 (EU-ARCCS)]
Line 936: Line 981:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Non-randomized</span>
 
border-style:solid;">Non-randomized</span>
 +
|
 +
|
 +
|
 
|
 
|
 
|-
 
|-
Line 945: Line 993:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|9% (95% CI 7 - 13)
+
|9% (95% CI 7-13%)
 
|[[Renal_cancer#Axitinib_.28Inlyta.29|Axitinib]]
 
|[[Renal_cancer#Axitinib_.28Inlyta.29|Axitinib]]
−
|19% (95% CI 15 - 24)
+
|19% (95% CI 15-24%)
 
|Treatment exposed (sunitinib, cytokines)
 
|Treatment exposed (sunitinib, cytokines)
 
|-
 
|-
Line 957: Line 1,005:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|15% (95% CI NR)
+
|15%
 
|[[Renal_cancer#Axitinib_.28Inlyta.29|Axitinib]]
 
|[[Renal_cancer#Axitinib_.28Inlyta.29|Axitinib]]
−
|32% (95% CI NR)
+
|32%
 
|Treatment naive
 
|Treatment naive
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 
*[[Sorafenib (Nexavar)]] 400 mg PO BID
 
*[[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
 
**Can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity
Line 999: Line 1,048:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|31% (95% CI NR)
+
|31%
 
|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
 
|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]
−
|6% (95% CI NR)
+
|6%
 
|Treatment naive
 
|Treatment naive
 
|-
 
|-
Line 1,011: Line 1,060:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Non-randomized</span>
 
border-style:solid;">Non-randomized</span>
−
|10% (95% CI NR)
+
|10%
 +
|
 +
|
 +
|
 
|-
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970162-7/fulltext Gore et al. 2009]
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970162-7/fulltext Gore et al. 2009]
Line 1,020: Line 1,072:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Non-randomized</span>
 
border-style:solid;">Non-randomized</span>
−
|17% (95% CI NR)
+
|17%
 +
|
 +
|
 +
|
 
|-
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 Motzer et al. 2013]
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1303989 Motzer et al. 2013]
Line 1,029: Line 1,084:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|25% (95% CI 21 - 28)
+
|25% (95% CI 21-28%)
 
|[[Renal_cancer#Pazopanib_.28Votrient.29|Pazopanib]]
 
|[[Renal_cancer#Pazopanib_.28Votrient.29|Pazopanib]]
−
|31% (95% CI 27 - 34)
+
|31% (95% CI 27-34%)
 
|Treatment naive
 
|Treatment naive
 
|-
 
|-
Line 1,043: Line 1,098:
 
|
 
|
 
|[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
 
|[[Renal_cancer#Everolimus_.28Afinitor.29|Everolimus]]
 +
|
 +
|
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Sunitinib (Sutent)]] 50 mg PO once per day on days 1 to 28
 
*[[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  
 
**Dose may be decreased to [[Sunitinib (Sutent)]] 37.5 mg or 25 mg PO once per day depending on tolerability  
Line 1,059: Line 1,116:
 
# 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, 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]
 
# 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. doi: 10.1056/NEJMc1400731. [http://www.nejm.org/doi/full/10.1056/NEJMc1400731 link to letter] [http://www.ncbi.nlm.nih.gov/pubmed/24785224 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}}==
 
==Temsirolimus (Torisel) {{#subobject:8160ec|Regimen=1}}==
Line 1,082: Line 1,139:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
−
|8.6% (95% CI 4.8 - 12.4)
+
|9% (95% CI 5-12%)
 
|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]<br> Interferon alfa-2a & Temsirolimus
 
|[[Renal_cancer#Interferon_alfa-2a_.28Roferon-A.29|Interferon alfa-2a]]<br> Interferon alfa-2a & Temsirolimus
−
|4.8% (95% CI 1.9 - 7.8)<br>8.1% (95% CI 4.4-11.8)
+
|5% (95% CI 2-8%)<br>8% (95% CI 4-12%)
 
|Treatment naive
 
|Treatment naive
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per week
  
−
*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once every week
+
====Supportive medications====
−
 
 
−
Supportive medications:
 
 
*[[Diphenhydramine (Benadryl)]] or similar H1 blocker 25 to 50 mg IV once 30 minutes prior to temsirolimus
 
*[[Diphenhydramine (Benadryl)]] or similar H1 blocker 25 to 50 mg IV once 30 minutes prior to temsirolimus
  

Revision as of 00:56, 5 August 2016

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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.

14 regimens on this page
22 variants on this page


Metastatic disease

Axitinib (Inlyta)

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Regimen

Study Evidence ORR Comparator Comparator ORR Pt Population
Rini et al. 2011 (AXIS) Phase III 19% (95% CI 15-24%) Sorafenib 9% (95% CI 7-13%) Treatment exposed (sunitinib, cytokines)
Hutson et al. 2013 Phase III 32% Sorafenib 15% Treatment naive

Chemotherapy

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

References

  1. 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
  2. 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 Pt Population
Bukowski et al. 2007 Randomized Phase II 13% Bevacizumab & Erlotinib 14% Treatment naive

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

  1. 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

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

References

  1. 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

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

  1. 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
  2. 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

Cabozantinib (Cabometyx)

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Regimen

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

Chemotherapy

Used as long as clinical benefit was perceived or unacceptable toxicity

References

  1. 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

Erlotinib (Tarceva)

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Regimen

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

Chemotherapy

‘’’Given until progression of disease or unacceptable toxicity

References

  1. 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 ORR Comparator Comparator ORR Pt Population
Motzer et al. 2008 (RECORD-1) Phase III 1% Placebo 0% Progessed after VEGFR TKI tx
Motzer et al. 2014 (RECORD-3) Randomized Phase II Sunitinib
Motzer et al. 2015 (CheckMate 025) Phase III 5% Nivolumab 25% Mixed pop; 72% had anti-angiogenic therapy
Choueiri et al. 2015 (METEOR) Phase III 5% (95% CI 2-9%) Cabozantinib 21% (95% CI 16-28%) Progressed after VEGFR TKI tx
Motzer et al. 2015 Randomized Phase II Everolimus & Lenvatinib
Lenvatinib

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

  1. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. Epub 2008 Jul 22. 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
  2. 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
  3. 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
  4. 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
  5. 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 Pt Population
Motzer et al. 2015 Randomized Phase II 43% (95% CI 29-58%) Everolimus
Lenvatinib 		6% (95% CI 1-17%)
27% (95% CI 16-41%) 		progressed after VEGFR TKI tx

Chemotherapy

Continued until progression or unacceptable toxicity

References

  1. 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

Gemcitabine & Doxorubicin

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Regimen

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

Chemotherapy

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

References

  1. 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

21-day cycles

Regimen #2

Study Evidence
Pandya et al. 2011 Retrospective

Chemotherapy

21-day cycles

References

  1. 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
  2. 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

Regimen #1

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

Immunotherapy

28-day cycle for up to 3 cycles

Supportive medications

Regimen #2

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

Immunotherapy

8-week cycle for up to 2 cycles

Regimen #3

Study Evidence
Klapper et al. 2008 Retrospective

Immunotherapy

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

  1. 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 contains verified protocol PubMed
  2. 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
  3. 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

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

8-week cycle for up to 2 cycles

References

  1. 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 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 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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

Lenvatinib (Lenvima)

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Regimen

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

Chemotherapy

Continued until progression or unacceptable toxicity

References

  1. 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 Pt Population
Motzer et al. 2015 (CheckMate 025) Phase III 25% Everolimus 5% Mixed pop; 72% had anti-angiogenic therapy

Immunotherapy

14-day cycles

References

  1. 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

Pazopanib (Votrient)

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Regimen

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

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

  1. 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
  2. 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
  3. 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
  4. 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
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

  1. 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
  2. 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
  3. 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

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

References

  1. 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 Pt Population
Escudier et al. 2007 (TARGET) Phase III 10% Placebo 2% Treated with cytokines previously
Escudier et al. 2009 Randomized Phase II Interferon alfa-2a
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%) Treatment exposed (sunitinib, cytokines)
Hutson et al. 2013 Phase III 15% Axitinib 32% Treatment naive

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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 Pt Population
Motzer et al. 2007 Phase III 31% Interferon alfa-2a 6% Treatment naive
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%) Treatment naive
Motzer et al. 2014 (RECORD-3) Randomized Phase II Everolimus

Chemotherapy

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

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

Temsirolimus (Torisel)

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Regimen

Study Evidence ORR Comparator Comparator ORR Pt Population
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%) 		Treatment naive

Chemotherapy

Supportive medications

References

  1. 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
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