Difference between revisions of "Renal cell carcinoma"
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− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | < | + | [[#top|Back to Top]] |
− | < | + | </div> |
− | + | {{#lst:Editorial board transclusions|rcc}} | |
− | + | ''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Renal_cell_carcinoma_-_historical|historical regimens page]] or to a histology- or biomarker-specific page. For placebo or observational studies in this condition, please visit [[Renal cell carcinoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''<br> | |
− | + | '''Note: This page contains trials that did not specify histology or allowed patients with multiple histologies. Trials limited to a specific histology including those that required a clear-cell component are on dedicated pages:''' | |
− | + | *'''Histology-specific:''' | |
− | + | **'''[[Clear cell renal cell carcinoma]]''' | |
− | | | + | **'''[[Non-clear cell renal cell carcinoma]]''' |
+ | ***'''[[Papillary renal cell carcinoma]]''' | ||
+ | ***'''[[Sarcomatoid renal cell carcinoma]]''' | ||
+ | *'''Biomarker-specific:''' | ||
+ | **'''[[Renal_cell_carcinoma,_VHL-associated|RCC, VHL-associated]]''' | ||
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+ | =Living Interactive Systematic Reviews= | ||
+ | *[https://adjrcc.network-meta-analysis.com/ Adjuvant treatment options in renal cell carcinoma] | ||
+ | *[https://rcc.network-meta-analysis.com/RCC.html Metastatic renal cell carcinoma (mRCC)] | ||
=Guidelines= | =Guidelines= | ||
− | == | + | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' |
− | *'''2016:''' [ | + | ==[https://www.esmo.org/ ESMO]== |
+ | *'''2021:''' Kanesveran et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8645910/ Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma] [https://pubmed.ncbi.nlm.nih.gov/34864348/ PubMed] | ||
+ | *'''2021:''' Powles et al. [https://doi.org/10.1016/j.annonc.2021.09.014 ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma] [https://pubmed.ncbi.nlm.nih.gov/34597799/ PubMed] | ||
+ | *'''2024:''' Powles et al. [https://doi.org/10.1016/j.annonc.2024.05.537 Renal cell carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/38788900/ PubMed] | ||
+ | **'''2019:''' Escudier et al. [https://doi.org/10.1093/annonc/mdz056 Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/30788497/ PubMed] | ||
+ | **'''2016:''' Escudier et al. [https://doi.org/10.1093/annonc/mdw328 Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/27664262/ PubMed] | ||
+ | **'''2014:''' Escudier et al. [https://doi.org/10.1093/annonc/mdu259 Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/25210086/ PubMed] | ||
+ | **'''2012:''' Escudier et al. [https://doi.org/10.1093/annonc/mds227 Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/22997456/ PubMed] | ||
+ | **'''2010:''' Escudier & Kataja. [https://doi.org/10.1093/annonc/mdq206 Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555064/ PubMed] | ||
+ | **'''2009:''' Escudier & Kataja. [https://doi.org/10.1093/annonc/mdp137 Renal cell carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454473/ PubMed] | ||
− | == | + | ==ISRS== |
− | *''' | + | *'''2024:''' Siva et al. [https://doi.org/10.1016/s1470-2045(23)00513-2 Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS)] [https://pubmed.ncbi.nlm.nih.gov/38181809/ PubMed] |
− | ==[https://www.nccn.org/ NCCN] | + | ==NCCN== |
− | *[https://www. | + | *[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1440 NCCN Guidelines - Kidney Cancer] |
+ | *'''2022:''' Motzer et al. [https://doi.org/10.6004/Jnccn.2022.0001 Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10191161/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34991070/ PubMed] | ||
+ | *'''2017:''' Motzer et al. [https://doi.org/10.6004/jnccn.2017.0100 Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology] [https://pubmed.ncbi.nlm.nih.gov/28596261/ PubMed] | ||
+ | *'''2015:''' Motzer et al. [https://doi.org/10.6004/jnccn.2015.0022 Kidney Cancer, Version 3.2015] [https://pubmed.ncbi.nlm.nih.gov/25691606/ PubMed] | ||
+ | *'''2014:''' Motzer et al. [https://doi.org/10.6004/jnccn.2014.0018 Kidney cancer, version 2.2014] [https://pubmed.ncbi.nlm.nih.gov/24586079/ PubMed] | ||
+ | *'''2011:''' Motzer et al. [https://doi.org/10.6004/Jnccn.2011.0082 Kidney cancer.] [https://pubmed.ncbi.nlm.nih.gov/21917622/ PubMed] | ||
+ | *'''2009:''' Motzer et al. [https://doi.org/10.6004/Jnccn.2009.0043 NCCN clinical practice guidelines in oncology: kidney cancer.] [https://pubmed.ncbi.nlm.nih.gov/19555584/ PubMed] | ||
+ | *'''2006:''' Motzer et al. [https://doi.org/10.6004/Jnccn.2006.0089 Kidney cancer. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/17112454/ PubMed] | ||
+ | *'''2005:''' Motzer et al. Kidney cancer. Clinical practice guidelines. [https://pubmed.ncbi.nlm.nih.gov/19813325/ PubMed] | ||
− | = | + | ==[https://siog.org/ SIOG]== |
− | + | *'''2018:''' Kanesvaran et al. [https://doi.org/10.1016/S1470-2045(18)30125-6 Elderly patients with metastatic renal cell carcinoma: position paper from the International Society of Geriatric Oncology] [https://pubmed.ncbi.nlm.nih.gov/29893263/ PubMed] | |
− | + | ==SITC== | |
− | + | *'''2019:''' Rini et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6924043/ The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC)] [https://pubmed.ncbi.nlm.nih.gov/31856918/ PubMed] | |
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− | = | + | =Risk Stratification Calculators= |
− | + | *[https://www.mdcalc.com/heng-score-metastatic-renal-cell-carcinoma-rcc-prognosis International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) calculator] | |
− | + | **ref: Heng DY, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN, Mackenzie M, Wood L, Donskov F, Tan MH, Rha SY, Agarwal N, Kollmannsberger C, Rini BI, Choueiri TK; External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013 Feb;14(2):141-8. Epub 2013 Jan 9. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144042/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23312463/ PubMed] | |
− | + | *[https://www.mdcalc.com/memorial-sloan-kettering-cancer-center-mskcc-motzer-score-metastatic-renal-cell-carcinoma-rcc Memorial Sloan Kettering Cancer Center (MSKCC) calculator] | |
− | + | **ref: Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002 Jan 1;20(1):289-96. [https://doi.org/10.1200/JCO.2002.20.1.289?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed link to original article] [https://pubmed.ncbi.nlm.nih.gov/11773181/ PubMed] | |
− | + | *[https://rgulati.shinyapps.io/rcc-risk-calculator/ Mortality and complication risk calculator for a patients with clinical T1 renal cortical mass up to 7 cm] (Dr. Sarah P. Psutka) | |
− | + | **ref: Psutka SP et al., A clinical decision aid to support personalized treatment selection for patients with stage T1 renal masses: Results from a multi-institutional competing risks analysis including performance status and comorbidity. Working paper. [https://www.urotoday.com/conference-highlights/asco-gu-2020/asco-gu-2020-kidney-cancer/119296-asco-gu-2020-a-novel-clinical-decision-aid-to-support-personalized-treatment-selection-for-patients-with-ct1-renal-cortical-masses-results-from-a-multi-institutional-competing-risks-analysis-including-performance-status-and-comorbidity.html link to news article] | |
− | + | *[https://www.mdcalc.com/ucla-integrated-staging-system-uiss-renal-cell-carcinoma-rcc UCLA Integrated Staging System (UISS) for Renal Cell Carcinoma (RCC)] | |
− | + | **ref: Zisman A, Pantuck AJ, Dorey F, Said JW, Shvarts O, Quintana D, Gitlitz BJ, deKernion JB, Figlin RA, Belldegrun AS. Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol. 2001 Mar 15;19(6):1649-57. [https://pubmed.ncbi.nlm.nih.gov/11250993/ PubMed] | |
− | + | *Leibovich prognostic model | |
− | + | **ref: Leibovich BC, Lohse CM, Cheville JC, Zaid HB, Boorjian SA, Frank I, Thompson RH, Parker WP. Predicting Oncologic Outcomes in Renal Cell Carcinoma After Surgery. Eur Urol. 2018 May;73(5):772-780. Epub 2018 Feb 3. [https://pubmed.ncbi.nlm.nih.gov/29398265/ PubMed] | |
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+ | =Adjuvant therapy= | ||
==Sunitinib monotherapy {{#subobject:cf6852|Regimen=1}}== | ==Sunitinib monotherapy {{#subobject:cf6852|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
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===Regimen {{#subobject:3c0a01|Variant=1}}=== | ===Regimen {{#subobject:3c0a01|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | ! style="width: 20%" |Study |
− | ! | + | ! style="width: 20%" |Dates of enrollment |
− | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | ! style="width: 20%" |Comparator | |
− | ! | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
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− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878938/ Haas et al. 2016 (ECOG-ACRIN E2805)] |
− | |style="background-color:#1a9851"|Phase | + | |2006-2010 |
− | |[[#Placebo|Placebo]] | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | + | |1. [[Renal_cell_carcinoma_-_null_regimens#Placebo|Placebo]]<br>2. [[#Sorafenib_monotherapy_999|Sorafenib]] | |
− | |style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Surgery | + | *[[Surgery#Renal_cell_carcinoma_surgery|Surgery]] |
− | ==== | + | </div> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
*[[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 | ||
− | + | '''42-day cycle for up to 9 cycles (1 year)''' | |
− | '''42-day | + | </div></div> |
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===References=== | ===References=== | ||
− | # '''ECOG-ACRIN E2805:''' Haas NB, Manola J, Uzzo RG, Flaherty KT, Wood CG, Kane C, Jewett M, Dutcher JP, Atkins MB, Pins M, Wilding G, Cella D, Wagner L, Matin S, Kuzel TM, Sexton WJ, Wong YN, Choueiri TK, Pili R, Puzanov I, Kohli M, Stadler W, Carducci M, Coomes R, DiPaola RS. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016 May 14;387(10032):2008-16. Epub 2016 Mar 9. Erratum in: Lancet. 2016 May 14;387(10032):1998. [https:// | + | #'''ECOG-ACRIN E2805:''' Haas NB, Manola J, Uzzo RG, Flaherty KT, Wood CG, Kane C, Jewett M, Dutcher JP, Atkins MB, Pins M, Wilding G, Cella D, Wagner L, Matin S, Kuzel TM, Sexton WJ, Wong YN, Choueiri TK, Pili R, Puzanov I, Kohli M, Stadler W, Carducci M, Coomes R, DiPaola RS. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016 May 14;387(10032):2008-16. Epub 2016 Mar 9. Erratum in: Lancet. 2016 May 14;387(10032):1998. [https://doi.org/10.1016/S0140-6736(16)00559-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878938/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26969090/ PubMed] [https://clinicaltrials.gov/study/NCT00326898 NCT00326898] |
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=Metastatic disease, first-line= | =Metastatic disease, first-line= | ||
− | == | + | ==Atezolizumab & Bevacizumab {{#subobject:af0d04|Regimen=1}}== |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:34c462|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | ! style="width: 20%" |Study | |
− | + | ! style="width: 20%" |Dates of enrollment | |
− | ===Regimen {{#subobject: | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ! style="width: 20%" |Comparator |
− | ! | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
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− | | | + | |[https://doi.org/10.1016/S0140-6736(19)30723-8 Rini et al. 2019 (IMmotion151)] |
− | + | |2015-05-20 to 2016-10-12 | |
− | + | | style="background-color:#1a9851" |Phase 3 (E-esc) | |
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− | |style="background-color:#1a9851"|Phase | ||
|[[#Sunitinib_monotherapy_2|Sunitinib]] | |[[#Sunitinib_monotherapy_2|Sunitinib]] | ||
− | |style="background-color:#91cf60"|Seems to have superior PFS | + | | style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup> (co-primary endpoint)<br>Median PFS: 11.2 vs 7.7 mo<br>(HR 0.74, 95% CI 0.57-0.96) |
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|} | |} | ||
− | + | ''<sup>1</sup>Reported efficacy is for the PD-L1-positive subgroup, which was the predefined co-primary endpoint.''<br> | |
− | + | ''Note: patients could have clear cell or sarcomatoid histology.'' | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ''' | + | ====Immunotherapy==== |
− | + | *[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1 | |
− | + | ====Targeted therapy==== | |
− | + | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | |
− | + | '''21-day cycles''' | |
− | + | </div></div> | |
− | + | ===References === | |
− | + | #'''IMmotion151:''' Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. Epub 2019 May 9. [https://doi.org/10.1016/S0140-6736(19)30723-8 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31079938/ PubMed] [https://clinicaltrials.gov/study/NCT02420821 NCT02420821] | |
− | + | ##'''Update:''' Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Alekseev BY, Lee JL, Suarez C, Stroyakovskiy D, De Giorgi U, Donskov F, Mellado B, Banchereau R, Hamidi H, Khan O, Craine V, Huseni M, Flinn N, Dubey S, Rini BI. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022 Feb 1;8(2):275-280. [https://doi.org/10.1001/jamaoncol.2021.5981 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855230/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34940781/ PubMed] | |
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− | ===References=== | ||
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==Everolimus monotherapy {{#subobject:b3af63|Regimen=1}}== | ==Everolimus monotherapy {{#subobject:b3af63|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
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===Regimen {{#subobject:474ade|Variant=1}}=== | ===Regimen {{#subobject:474ade|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | ! style="width: 20%" |Study |
− | ! | + | ! style="width: 20%" |Dates of enrollment |
− | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | |
− | ! | + | ! style="width: 20%" |Comparator |
− | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
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− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ Motzer et al. 2014 (RECORD-3)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |2009-2011 |
+ | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) | ||
|[[#Sunitinib_monotherapy_2|Sunitinib]] | |[[#Sunitinib_monotherapy_2|Sunitinib]] | ||
− | |style="background-color:# | + | | style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS (primary endpoint) |
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Targeted therapy==== | ||
*[[Everolimus (Afinitor)]] 10 mg PO once per day | *[[Everolimus (Afinitor)]] 10 mg PO once per day | ||
− | + | '''Continued indefinitely''' | |
− | + | </div> | |
− | ''' | + | <div class="toccolours" style="background-color:#cbd5e7"> |
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *RECORD-3: [[#Sunitinib_monotherapy_3|Sunitinib]] | + | *RECORD-3, upon progression: Second-line [[#Sunitinib_monotherapy_3|Sunitinib]] |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *Everolimus dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''RECORD-3:''' Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. [https://doi.org/10.1200/jco.2013.54.6911 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25049330/ PubMed] [https://clinicaltrials.gov/study/NCT00903175 NCT00903175] | |
− | # '''RECORD-3:''' Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. [ | ||
− | |||
− | |||
==Gemcitabine & Sunitinib {{#subobject:ec76af|Regimen=1}}== | ==Gemcitabine & Sunitinib {{#subobject:ec76af|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:py1|Variant=1}}=== | |
− | + | {| class="wikitable" style="width: 60%; text-align:center;" | |
− | + | ! style="width: 33%" |Study | |
− | === | + | ! style="width: 33%" |Dates of enrollment |
− | {| class="wikitable" style="width: | + | ! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !Study | ||
− | ![[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/cncr.29503 Michaelson et al. 2015 (MGH 07-212)] |
− | |style="background-color:#91cf61"|Phase | + | |2007-2013 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
*[[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''' | ||
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | # ''' | + | #'''MGH 07-212:''' Michaelson MD, McKay RR, Werner L, Atkins MB, Van Allen EM, Olivier KM, Song J, Signoretti S, McDermott DF, Choueiri TK. Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Cancer. 2015 Oct 1;121(19):3435-43. Epub 2015 Jun 8. [https://doi.org/10.1002/cncr.29503 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26058385/ PubMed] [https://clinicaltrials.gov/study/NCT00556049 NCT00556049] |
− | |||
− | |||
==High-dose Interleukin-2 {{#subobject:d95f4e|Regimen=1}}== | ==High-dose Interleukin-2 {{#subobject:d95f4e|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
HD IL-2: '''<u>H</u>'''igh-'''<u>D</u>'''ose '''<u>I</u>'''nter'''<u>L</u>'''eukin-'''<u>2</u>''' | HD IL-2: '''<u>H</u>'''igh-'''<u>D</u>'''ose '''<u>I</u>'''nter'''<u>L</u>'''eukin-'''<u>2</u>''' | ||
===Example orders=== | ===Example orders=== | ||
*[[Example orders for High-dose (HD) IL-2 in renal cancer]] | *[[Example orders for High-dose (HD) IL-2 in renal cancer]] | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | === | + | ===Regimen variant #1, 1.8 MU/kg/day, intermittent {{#subobject:ca472e|Variant=1}}=== |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | ! style="width: 20%" |Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |Dates of enrollment |
− | !Comparator | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence#Efficacy| | + | ! style="width: 20%" |Comparator |
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1001/jama.1994.03510360033032 Rosenberg et al. 1994] | ||
+ | |1985-1992 | ||
+ | | style="background-color:#91cf61" |Non-randomized | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1995.13.3.688 Fyfe et al. 1995] | ||
+ | |Not reported | ||
+ | | style="background-color:#91cf61" |Phase 2 (RT) | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2005.03.206 McDermott et al. 2005] |
− | |style="background-color:#1a9851"|Phase | + | | 1997-2000 |
− | |Subcutaneous IL-2 & Interferon | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:#d9ef8b"|Might have superior PFS | + | |[[#Interferon_alfa-2a_.26_Interleukin-2_999|Subcutaneous IL-2 & Interferon]] |
+ | | style="background-color:#d9ef8b" |Might have superior PFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====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 for up to 14 doses per week, on days 1 to 5, 15 to 19 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Ciprofloxacin (Cipro)]] 250 mg PO twice per day on days 1 to 10, 15 to 24 | |
− | |||
− | ====Supportive | ||
− | *[[Ciprofloxacin (Cipro)]] 250 mg PO | ||
*All antihypertensive therapy discontinued at least 24 hours before each cycle | *All antihypertensive therapy discontinued at least 24 hours before each cycle | ||
*[[Acetaminophen (Tylenol)]] 650 mg PO every 4 hours | *[[Acetaminophen (Tylenol)]] 650 mg PO every 4 hours | ||
Line 491: | Line 226: | ||
*[[Meperidine (Demerol)]] 25 to 50 mg PO every 6 hours for chills and rigors | *[[Meperidine (Demerol)]] 25 to 50 mg PO every 6 hours for chills and rigors | ||
*"An antidiarrheal agent, antiemetics, anxiolytics, diuretics, and vasopressors as needed" | *"An antidiarrheal agent, antiemetics, anxiolytics, diuretics, and vasopressors as needed" | ||
− | + | '''28-day cycle for up to 3 cycles''' | |
− | === | + | </div></div><br> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | !Study | + | ===Regimen variant #2, 2.16 MU/kg/day, intermittent, goal 10.8 MU {{#subobject:9867a|Variant=1}}=== |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Comparator | + | ! style="width: 20%" |Study |
− | ![[Levels_of_Evidence# | + | ! style="width: 20%" |Dates of enrollment |
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | | rowspan="2" |[https://doi.org/10.1200/JCO.1994.12.8.1572 Yang et al. 1994] |
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | | rowspan="2" |1991-1993 |
− | |[[#Low-dose_Interleukin-2|LD IL-2 (IV)]] | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:#91cf60"|Seems to have superior ORR | + | |1. [[#Low-dose_Interleukin-2|LD IL-2 (IV)]] |
+ | | style="background-color:#91cf60" |Seems to have superior ORR | ||
|- | |- | ||
− | |[[#Low-dose_Interleukin-2|LD IL-2 (SC)]] | + | |2. [[#Low-dose_Interleukin-2|LD IL-2 (SC)]] |
− | |style="background-color:#91cf60"|Seems to have superior ORR | + | | style="background-color:#91cf60" |Seems to have superior ORR |
|- | |- | ||
|} | |} | ||
+ | ''Note: reported efficacy is based on the 2003 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours for up to 15 doses | *[[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 | + | **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 |
− | |||
'''8-week cycle for up to 2 cycles''' | '''8-week cycle for up to 2 cycles''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #3, 5 MU/m<sup>2</sup>/day, CI {{#subobject:bd04b6|Variant=1}}=== |
− | !Study | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |Study |
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/JCO.1999.17.8.2521 Figlin et al. 1999] |
− | |style="background-color:# | + | |1994-1997 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Interleukin-2_.26_TILs_999|IL-2 & CD8+ TILs]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] | + | *[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 5,000,000 units/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on days 1, 8, 15, 22 (total dose per cycle: 80 MU/m<sup>2</sup>) |
− | + | '''8-week cycles''' | |
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | # | + | #Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994 Mar 23-30;271(12):907-13. [https://doi.org/10.1001/jama.1994.03510360033032 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8120958/ 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. [ | + | #Yang JC, Topalian SL, Parkinson D, Schwartzentruber DJ, Weber JS, Ettinghausen SE, White DE, Steinberg SM, Cole DJ, Kim HI, Levin R, Guleria A, MacFarlane MP, White RL, Einhorn JH, Seipp CA, Rosenberg SA. Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J Clin Oncol. 1994 Aug;12(8):1572-6. [https://doi.org/10.1200/JCO.1994.12.8.1572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8040669/ PubMed] |
− | # | + | ##'''Update:''' Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003 Aug 15;21(16):3127-32. [https://doi.org/10.1200/jco.2003.02.122 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275327/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12915604/ PubMed] |
− | # | + | #Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995 Mar;13(3):688-96. [https://doi.org/10.1200/JCO.1995.13.3.688 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7884429/ PubMed] |
− | + | #Figlin RA, Thompson JA, Bukowski RM, Vogelzang NJ, Novick AC, Lange P, Steinberg GD, Belldegrun AS. Multicenter, randomized, phase III trial of CD8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol. 1999 Aug;17(8):2521-9. [https://doi.org/10.1200/JCO.1999.17.8.2521 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10561318/ PubMed] | |
+ | #McDermott DF, Regan MM, Clark JI, Flaherty LE, Weiss GR, Logan TF, Kirkwood JM, Gordon MS, Sosman JA, Ernstoff MS, Tretter CP, Urba WJ, Smith JW, Margolin KA, Mier JW, Gollob JA, Dutcher JP, Atkins MB. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol. 2005 Jan 1;23(1):133-41. [https://doi.org/10.1200/jco.2005.03.206 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15625368/ PubMed] | ||
==Low-dose Interleukin-2 {{#subobject:a2e938|Regimen=1}}== | ==Low-dose Interleukin-2 {{#subobject:a2e938|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
LD IL-2: '''<u>L</u>'''ow-'''<u>D</u>'''ose '''<u>I</u>'''nter'''<u>L</u>'''eukin-'''<u>2</u>''' | LD IL-2: '''<u>L</u>'''ow-'''<u>D</u>'''ose '''<u>I</u>'''nter'''<u>L</u>'''eukin-'''<u>2</u>''' | ||
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #1, Intravenous {{#subobject:445b6c|Variant=1}}=== |
− | !Study | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |Study |
− | !Comparator | + | ! style="width: 20%" |Dates of enrollment |
− | ![[Levels_of_Evidence# | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
+ | ! style="width: 20%" | Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | | rowspan="2" |[https://doi.org/10.1200/JCO.1994.12.8.1572 Yang et al. 1994] |
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | | rowspan="2" | 1991-1993 |
− | |[[#High-dose_Interleukin-2|High-dose IL-2]] | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-de-esc) |
− | |style="background-color:#fc8d59"|Seems to have inferior ORR | + | |1. [[#High-dose_Interleukin-2|High-dose IL-2]] |
+ | | style="background-color:#fc8d59" |Seems to have inferior ORR | ||
|- | |- | ||
− | | | + | |2. [[#Low-dose_Interleukin-2|LD IL-2]]; SC |
− | |style="background-color:#d3d3d3"|Not reported | + | | style="background-color:#d3d3d3" |Not reported |
|- | |- | ||
|} | |} | ||
+ | ''Note: efficacy is based on the 2003 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 72,000 units/kg IV every 8 hours for up to 15 doses | + | *[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] as follows: |
− | **Then after 7 to 10 days of rest | + | **Week 1: 72,000 units/kg IV every 8 hours for up to 15 doses |
− | + | **Then after 7 to 10 days of rest: 72,000 units/kg IV every 8 hours for up to 15 doses is given again | |
'''8-week cycle for up to 2 cycles''' | '''8-week cycle for up to 2 cycles''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #2, Subcutaneous {{#subobject:cbb5b2|Variant=1}}=== |
− | !Study | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |Study |
− | !Comparator | + | ! style="width: 20%" |Dates of enrollment |
− | ![[Levels_of_Evidence# | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | | rowspan="2" |[https://doi.org/10.1200/JCO.1994.12.8.1572 Yang et al. 1994] |
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | | rowspan="2" |1991-1993 |
− | |[[#High-dose_Interleukin-2|High-dose IL-2]] | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-de-esc) |
− | |style="background-color:#fc8d59"|Seems to have inferior ORR | + | |1. [[#High-dose_Interleukin-2|High-dose IL-2]] |
+ | | style="background-color:#fc8d59" |Seems to have inferior ORR | ||
|- | |- | ||
− | | | + | |2. [[#Low-dose_Interleukin-2|LD IL-2]]; IV |
− | |style="background-color:#d3d3d3"|Not reported | + | | style="background-color:#d3d3d3" |Not reported |
|- | |- | ||
|} | |} | ||
+ | ''Note: this arm was added to the trial after the interim results were announced in 1994.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 250,000 units/kg SC once per day for 5 days | + | *[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] as follows: |
− | ** | + | **Week 1: 250,000 units/kg SC once per day for 5 days |
− | + | **Weeks 2 to 6: 125,000 units/kg SC once per day for 5 days per week | |
'''8-week cycle for up to 2 cycles''' | '''8-week cycle for up to 2 cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [ | + | #Yang JC, Topalian SL, Parkinson D, Schwartzentruber DJ, Weber JS, Ettinghausen SE, White DE, Steinberg SM, Cole DJ, Kim HI, Levin R, Guleria A, MacFarlane MP, White RL, Einhorn JH, Seipp CA, Rosenberg SA. Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J Clin Oncol. 1994 Aug;12(8):1572-6. [https://doi.org/10.1200/JCO.1994.12.8.1572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8040669/ PubMed] |
− | + | ##'''Update:''' Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003 Aug 15;21(16):3127-32. [https://doi.org/10.1200/jco.2003.02.122 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275327/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12915604/ PubMed] | |
==Interferon alfa-2a monotherapy {{#subobject:8f04d6|Regimen=1}}== | ==Interferon alfa-2a monotherapy {{#subobject:8f04d6|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 5 MU 5x per week {{#subobject:f49d4e|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" | Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/oxfordjournals.annonc.a059097 Sagaster et al. 1995] | ||
+ | |Not reported-1992 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cimetidine.2C_Coumarin.2C_Interferon_alfa-2a_999|Cimetidine, Coumarin, IFN alfa-2a]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
− | |||
|} | |} | ||
− | === | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ====Immunotherapy==== |
− | ! | + | *[[Interferon alfa-2a (Roferon-A)]] 5,000,000 units SC once per day on days 1 to 5 (5 times per week) |
− | + | '''7-day cycles''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ||
− | + | ===Regimen variant #2, 9 MU TIW {{#subobject:524ccc|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | ! style="width: 20%" |Study | |
− | + | ! style="width: 20%" |Dates of enrollment | |
− | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | ! style="width: 20%" |Comparator | |
− | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |[[# | ||
− | |||
− | |||
− | |||
− | |||
− | |[[# | ||
− | |||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835851/ Gore et al. 2010 (MRC RE04/EORTC GU 30012)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835851/ Gore et al. 2010 (MRC RE04/EORTC GU 30012)] | ||
− | |style="background-color:#1a9851"|Phase | + | |2001-2006 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:#ffffbf"| | + | |[[#Fluorouracil.2C_Interferon_alfa-2a.2C_Interleukin-2_999|5-FU, Interferon alfa-2a, IL-2]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1158/1078-0432.ccr-15-0580 Hawkins et al. 2016 (Active Biotech 06762004)] |
− | |style="background-color:#1a9851"|Phase | + | |2007-2010 |
− | |Naptumomab estafenatox + IFNα | + | | style="background-color:#1a9851" |Phase 2/3 (C) |
− | |style="background-color:#ffffbf"| | + | |[[#Naptumomab estafenatox_.26_Interferon_alfa_999|Naptumomab estafenatox + IFNα]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Interferon alfa-2a (Roferon-A)]] 9 | + | *[[Interferon alfa-2a (Roferon-A)]] 9,000,000 units SC 3 times per week |
− | |||
− | |||
'''Given for varying lengths of time; see individual trials''' | '''Given for varying lengths of time; see individual trials''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *Some protocols: Dose can be reduced to 3,000,000 or 6,000,000 units SC 3 times per week based on tolerability | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | === | + | ===Regimen variant #3, 9 MU daily, with lead-in {{#subobject:5f04fc|Variant=1}}=== |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | ! style="width: 20%" | Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |Dates of enrollment |
− | !Comparator | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | ! style="width: 20%" |Comparator |
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2000.18.16.2972 Motzer et al. 2000] |
− | |style="background-color:#1a9851"|Phase | + | |1994-1996 |
− | |[[# | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Interferon_alfa_.26_13-CRA_999|IFN alfa & 13-CRA]] |
+ | | style="background-color:#ffffbf" | Did not meet primary endpoint of ORR | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: Interferon alfa-2a dose was increased only if the prior dose was tolerated.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Interferon alfa-2a (Roferon-A)]] as follows: | *[[Interferon alfa-2a (Roferon-A)]] as follows: | ||
− | ** | + | **Cycle 1: 3,000,000 units SC once per day on days 1 to 7 |
− | ** | + | **Cycle 2: 6,000,000 units SC once per day on days 1 to 7 |
− | ** | + | **Cycle 3 onwards: 9,000,000 units SC once per day on days 1 to 7 |
− | + | '''7-day cycles''' | |
− | ''' | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | === | + | ===Regimen variant #4, 10 MU TIW, with lead-in {{#subobject:leadd5|Variant=1}}=== |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | ! style="width: 20%" |Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |Dates of enrollment |
− | !Comparator | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | ! style="width: 20%" |Comparator |
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(98)03544-2 Ritchie et al. 1999 (MRC RE01)] |
− | |style="background-color:#1a9851"|Phase | + | |1992-1997 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
− | |style="background-color:# | + | |[[Renal_cell_carcinoma_-_historical#Medroxyprogesterone_acetate_monotherapy|MPA]] |
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 8.5 vs 6 mo<br>(HR 0.72, 95% CI 0.55-0.94) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Interferon alfa-2a (Roferon-A)]] 10 | + | *[[Interferon alfa-2a (Roferon-A)]] as follows: |
− | + | **Cycle 1: 5,000,000 units SC once per day on days 1 & 3, then 10,000,000 units SC once on day 5 | |
− | ''' | + | **Cycles 2 to 12: 10,000,000 units SC once per day on days 1, 3, 5 (3 times per week) |
− | + | '''7-day cycle for 12 cycles''' | |
− | === | + | </div></div><br> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | !Study | + | ===Regimen variant #5, 10 MU TIW {{#subobject:800dd5|Variant=1}}=== |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Comparator | + | ! style="width: 20%" |Study |
− | ![[Levels_of_Evidence# | + | ! style="width: 20%" |Dates of enrollment |
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835851/ Gore et al. 2010 (MRC RE04/EORTC GU 30012)] | |
− | | | + | |2001-2006 |
− | |Interferon alfa-2a | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | + | |[[#Fluorouracil.2C_Interferon_alfa-2a.2C_Interleukin-2_999|5-FU, Interferon alfa-2a, IL-2]] | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | |
− | |||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Interferon alfa-2a (Roferon-A)]] | + | *[[Interferon alfa-2a (Roferon-A)]] 10,000,000 units SC once per day on days 1, 3, 5 (3 times per week) |
− | + | '''7-day cycles''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | + | ===Regimen variant #6, 18 MU TIW, with lead-in {{#subobject:b28245|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | === | + | ! style="width: 20%" |Study |
− | # | + | ! style="width: 20%" |Dates of enrollment |
− | # | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | + | ! style="width: 20%" |Comparator | |
− | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | # | ||
− | |||
− | = | ||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1093/oxfordjournals.annonc.a058185 Fosså et al. 1992] |
− | | | + | |1985-1986 |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#Interferon_alfa-2a_.26_Vinblastine_999|IFN alfa-2a & Vinblastine]] | |
− | + | | style="background-color:#ffffbf" |Did not meet efficacy endpoints | |
− | |||
− | |||
− | |||
|- | |- | ||
− | |[ | + | | rowspan="2" |[https://doi.org/10.1056/NEJMoa066838 Hudes et al. 2007 (ARCC)] |
− | |style="background-color:#1a9851"|Phase | + | | rowspan="2" |2003-2005 |
− | |[[# | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |1. [[#Interferon_alfa-2a_.26_Temsirolimus_999|Interferon alfa-2a & Temsirolimus]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | | | + | |2. [[#Temsirolimus_monotherapy|Temsirolimus]] |
− | + | | style="background-color:#d73027" |Inferior OS | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | | | ||
|- | |- | ||
|} | |} | ||
− | ''Note: | + | ''Note: Interferon alfa-2a dose was increased only if the prior dose was tolerated.'' |
− | ====Immunotherapy | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Immunotherapy==== |
− | *[[ | + | *[[Interferon alfa-2a (Roferon-A)]] as follows: |
+ | **Cycle 1: 3,000,000 units SC once per day on days 1, 3, 5 | ||
+ | **Cycle 2: 9,000,000 units SC once per day on days 1, 3, 5 | ||
+ | **Cycle 3 onwards: 18,000,000 units SC once per day on days 1, 3, 5 | ||
+ | '''7-day cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *If higher doses cannot be tolerated, highest tolerable doses of 3,000,000, 4,500,500, or 6,000,000 units can be used | ||
+ | </div></div> | ||
+ | === References=== | ||
+ | # Fosså SD, Martinelli G, Otto U, Schneider G, Wander H, Oberling F, Bauer HW, Achtnicht U, Holdener EE. Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study. Ann Oncol. 1992 Apr;3(4):301-5. [https://doi.org/10.1093/oxfordjournals.annonc.a058185 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1390305/ PubMed] | ||
+ | # Sagaster P, Micksche M, Flamm J, Ludwig H. Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer. Ann Oncol. 1995 Dec;6(10):999-1003. [https://doi.org/10.1093/oxfordjournals.annonc.a059097 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8750152/ PubMed] | ||
+ | #'''MRC RE01:''' Ritchie A, Griffiths G, Parmar M; Medical Research Council Renal Cancer Collaborators. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Lancet. 1999 Jan 2;353(9146):14-7. [https://doi.org/10.1016/S0140-6736(98)03544-2 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10023944/ PubMed] | ||
+ | #Motzer RJ, Murphy BA, Bacik J, Schwartz LH, Nanus DM, Mariani T, Loehrer P, Wilding G, Fairclough DL, Cella D, Mazumdar M. Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol. 2000 Aug;18(16):2972-80. [https://doi.org/10.1200/JCO.2000.18.16.2972 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10944130/ PubMed] | ||
+ | #'''ARCC:''' Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. [https://doi.org/10.1056/NEJMoa066838 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17538086/ PubMed] [https://clinicaltrials.gov/study/NCT00065468 NCT00065468] | ||
+ | #'''MRC RE04/EORTC GU 30012:''' Gore ME, Griffin CL, Hancock B, Patel PM, Pyle L, Aitchison M, James N, Oliver RT, Mardiak J, Hussain T, Sylvester R, Parmar MK, Royston P, Mulders PF. Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial. Lancet. 2010 Feb 20;375(9715):641-8. Epub 2010 Feb 10. [https://doi.org/10.1016/S0140-6736(09)61921-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835851/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20153039/ PubMed] [https://clinicaltrials.gov/study/NCT00053820 NCT00053820] | ||
+ | #'''Active Biotech 06762004:''' Hawkins RE, Gore M, Shparyk Y, Bondar V, Gladkov O, Ganev T, Harza M, Polenkov S, Bondarenko I, Karlov P, Karyakin O, Khasanov R, Hedlund G, Forsberg G, Nordle Ö, Eisen T. A randomized phase II/III study of naptumomab estafenatox + IFNα versus IFNα in renal cell carcinoma: final analysis with baseline biomarker subgroup and trend analysis. Clin Cancer Res. 2016 Jul 1;22(13):3172-81. Epub 2016 Feb 5. [https://doi.org/10.1158/1078-0432.ccr-15-0580 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26851187/ PubMed] [https://clinicaltrials.gov/study/NCT00420888 NCT00420888] | ||
− | + | ==Sorafenib monotherapy {{#subobject:fe45b0|Regimen=1}}== | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ==== | + | ===Regimen {{#subobject:90ba4d|Variant=1}}=== |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | ! style="width: 20%" |Study | |
− | + | ! style="width: 20%" |Dates of enrollment | |
− | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | |
− | === | + | ! style="width: 20%" |Comparator |
− | {| class="wikitable" style=" | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | | | ||
|- | |- | ||
− | | | + | |[https://doi.org/10.1002/cncr.24864 Stadler et al. 2010 (ARCCS)] |
− | + | |2005-06 to 2006-07 | |
− | + | | style="background-color:#91cf61" |Non-randomized | |
− | + | | style="background-color:#d3d3d3" | | |
− | + | | style="background-color:#d3d3d3" | | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | = | ||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ejca.2018.11.001 Retz et al. 2018 (SWITCH-II)] |
− | + | |2012-06-14 to 2016-11-14 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#Pazopanib_monotherapy|Pazopanib]] | |
− | + | | style="background-color:#ffffbf" |Inconclusive whether non-inferior tPFS | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | | | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |style="background-color:#1a9851"|Phase | ||
− | |||
− | |[[# | ||
− | |||
− | |style="background-color:# | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Targeted therapy ==== |
− | + | *[[Sorafenib (Nexavar)]] 400 mg PO twice per day | |
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *Sorafenib can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment ==== | ||
+ | *SWITCH-II, upon progression: [[#Pazopanib_monotherapy_2|Pazopanib]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | #'''ARCCS:''' Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Bukowski RM; ARCCS Study Investigators. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. 2010 Mar 1;116(5):1272-80. [https://doi.org/10.1002/cncr.24864 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20082451/ PubMed] [https://clinicaltrials.gov/study/NCT00111020 NCT00111020] |
− | + | #'''SWITCH-II:''' Retz M, Bedke J, Bögemann M, Grimm MO, Zimmermann U, Müller L, Leiber C, Teber D, Wirth M, Bolenz C, van Alphen R, De Santis M, Beeker A, Lehmann J, Indorf M, Frank M, Bokemeyer C, Gschwend JE. SWITCH II: Phase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of advanced or metastatic renal cell carcinoma (AUO AN 33/11). Eur J Cancer. 2019 Jan;107:37-45. Epub 2018 Dec 7. [https://doi.org/10.1016/j.ejca.2018.11.001 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30529901/ PubMed] [https://clinicaltrials.gov/study/NCT01613846 NCT01613846] | |
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==Sunitinib monotherapy {{#subobject:b4a97a|Regimen=1}}== | ==Sunitinib monotherapy {{#subobject:b4a97a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:92e618|Variant=1}}=== | ===Regimen {{#subobject:92e618|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | ! style="width: 20%" |Study |
− | ! | + | ! style="width: 20%" |Dates of enrollment |
− | ![[Levels_of_Evidence# | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! | + | ! style="width: 20%" |Comparator |
− | |Comparator | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | ![[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/S1470-2045%2809%2970162-7 Gore et al. 2009 (A618-1037)] |
− | + | |2005-2007 | |
− | + | | style="background-color:#91cf61" | Non-randomized | |
− | + | | style="background-color:#d3d3d3" | | |
− | + | | style="background-color:#d3d3d3" | | |
− | |||
− | |||
− | |||
− | |style="background-color:#91cf61"|Non-randomized | ||
− | |||
− | |style="background-color:#d3d3d3"| | ||
− | |style="background-color:#d3d3d3"| | ||
− | |||
− | |||
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|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ Motzer et al. 2014 (RECORD-3)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |2009-2011 |
− | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) | |
|[[#Everolimus_monotherapy|Everolimus]] | |[[#Everolimus_monotherapy|Everolimus]] | ||
− | + | | style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS (primary endpoint) | |
− | |style="background-color:#ffffbf"|Inconclusive whether non-inferior | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.eururo.2015.04.017 Eichelberg et al. 2015 (SWITCH)] |
− | | | + | |2009-2011 |
− | + | | style="background-color:#1a9851" | Phase 3 (C) | |
− | + | |[[#Sorafenib_monotherapy|Sorafenib]] | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | |
− | |style="background-color:# | ||
− | |||
− | |||
− | |||
− | |||
− | |[[# | ||
− | |||
− | |style="background-color:# | ||
− | |||
− | |||
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− | |||
− | |||
− | |||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(19)30723-8 Rini et al. 2019 (IMmotion151)] |
− | | | + | |2015-05-20 to 2016-10-12 |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#Atezolizumab_.26_Bevacizumab|Atezolizumab & Bevacizumab]] | |
− | + | | style="background-color:#fc8d59" |Seems to have inferior PFS | |
− | |||
− | |||
− | |||
− | |style="background-color:#1a9851"|Phase | ||
− | |||
− | |[[# | ||
− | |||
− | | style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Targeted therapy==== | ||
*[[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 | ||
− | |||
− | |||
'''42-day cycles''' | '''42-day cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *SWITCH, upon progression: Second-line [[#Sorafenib_monotherapy_2|Sorafenib]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *Per some references, dose may be decreased to 37.5 mg or 25 mg PO once per day depending on tolerability | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''A618-1037:''' Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schöffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009 Aug;10(8):757-63. Epub 2009 Jul 15. [https://doi.org/10.1016/S1470-2045%2809%2970162-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19615940/ PubMed] [https://clinicaltrials.gov/study/NCT00130897 NCT00130897] | |
− | + | #'''PISCES:''' Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, Gschwend JE, De Giorgi U, Parikh O, Hawkins R, Sevin E, Négrier S, Khan S, Diaz J, Redhu S, Mehmud F, Cella D. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014 May 10;32(14):1412-8. Epub 2014 Mar 31. [https://doi.org/10.1200/JCO.2013.50.8267 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24687826/ PubMed] [https://clinicaltrials.gov/study/NCT01064310 NCT01064310] | |
− | + | #'''RECORD-3:''' Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. [https://doi.org/10.1200/jco.2013.54.6911 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25049330/ PubMed] [https://clinicaltrials.gov/study/NCT00903175 NCT00903175] | |
− | # '''A618-1037 :''' Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schöffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009 Aug;10(8):757-63. Epub 2009 Jul 15. [https:// | + | #'''SWITCH:''' Eichelberg C, Vervenne WL, De Santis M, Fischer von Weikersthal L, Goebell PJ, Lerchenmüller C, Zimmermann U, Bos MM, Freier W, Schirrmacher-Memmel S, Staehler M, Pahernik S, Los M, Schenck M, Flörcken A, van Arkel C, Hauswald K, Indorf M, Gottstein D, Michel MS. SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer. Eur Urol. 2015 Nov;68(5):837-47. Epub 2015 May 4. [https://doi.org/10.1016/j.eururo.2015.04.017 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25952317/ PubMed] [https://clinicaltrials.gov/study/NCT00732914 NCT00732914] |
− | + | #'''IMmotion151:''' Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. Epub 2019 May 9. [https://doi.org/10.1016/S0140-6736(19)30723-8 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31079938/ PubMed] [https://clinicaltrials.gov/study/NCT02420821 NCT02420821] | |
− | + | ##'''Update:''' Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Alekseev BY, Lee JL, Suarez C, Stroyakovskiy D, De Giorgi U, Donskov F, Mellado B, Banchereau R, Hamidi H, Khan O, Craine V, Huseni M, Flinn N, Dubey S, Rini BI. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022 Feb 1;8(2):275-280. [https://doi.org/10.1001/jamaoncol.2021.5981 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855230/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34940781/ PubMed] | |
− | # ''' | ||
− | |||
− | # '''RECORD-3:''' Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. [ | ||
− | |||
− | # ''' | ||
− | # ''' | ||
− | # ''' | ||
− | |||
==Temsirolimus monotherapy {{#subobject:8160ec|Regimen=1}}== | ==Temsirolimus monotherapy {{#subobject:8160ec|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | === Regimen {{#subobject:f56815|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | ! style="width: 20%" |Study | |
− | ===Regimen {{#subobject:f56815|Variant=1}}=== | + | ! style="width: 20%" |Dates of enrollment |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !Study | + | ! style="width: 20%" |Comparator |
− | ! | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | ![[Levels_of_Evidence# | ||
− | ! | ||
− | |Comparator | ||
− | ![[Levels_of_Evidence# | ||
|- | |- | ||
− | |rowspan=2|[ | + | | rowspan="2" |[https://doi.org/10.1056/NEJMoa066838 Hudes et al. 2007 (ARCC)] |
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | | rowspan="2" |2003-2005 |
− | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | |
− | |[[#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]] | + | |1. [[#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]] |
− | + | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 10.9 vs 7.3 mo<br>(HR 0.73, 95% CI 0.58-0.92) | |
− | |style="background-color:#1a9850"|Superior OS | ||
|- | |- | ||
− | | | + | |2. [[#Interferon_alfa-2a_.26_Temsirolimus_999|Interferon alfa-2a & Temsirolimus]] |
− | |Interferon alfa-2a & Temsirolimus | + | | style="background-color:#d3d3d3" |Not reported |
− | |||
− | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once | + | ====Targeted therapy==== |
− | + | *[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once on day 1 | |
− | ====Supportive | + | ====Supportive therapy==== |
− | *[[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 on day 1; 30 minutes prior to temsirolimus |
− | + | '''7-day cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''ARCC:''' Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. [ | + | #'''ARCC:''' Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. [https://doi.org/10.1056/NEJMoa066838 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17538086/ PubMed] [https://clinicaltrials.gov/study/NCT00065468 NCT00065468] |
=Metastatic disease, second-line= | =Metastatic disease, second-line= | ||
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==Cabozantinib monotherapy {{#subobject:pyr1|Regimen=1}}== | ==Cabozantinib monotherapy {{#subobject:pyr1|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:pyv1|Variant=1}}=== | ===Regimen {{#subobject:pyv1|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 1,124: | Line 648: | ||
|- | |- | ||
|} | |} | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | ! style="width: 20%" |Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |Dates of enrollment |
− | ! | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | + | ! style="width: 20%" | Comparator | |
− | ! | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | |||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017728/ Pal et al. 2023 (CONTACT-03)] |
− | |style="background-color:#1a9851"|Phase | + | |2020-07-28 to 2021-12-27 |
− | + | | style="background-color:#1a9851" | Phase 3 (C) | |
− | |[[# | + | |[[#Cabozantinib_.26_Atezolizumab_999|Cabozantinib & Atezolizumab]] |
− | | style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of PFS/OS |
− | |||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ==== | + | ====Targeted therapy==== |
− | *[[Cabozantinib (Cometriq)|Cabozantinib (Cabometyx)]] 60 mg PO once per day | + | *[[Cabozantinib (Cometriq)|Cabozantinib (Cabometyx)]] 60 mg PO once per day on days 1 to 28, taken at least 2 hours before or 1 hour after meals |
− | + | '''28-day cycles''' | |
− | + | </div></div> | |
− | ''' | ||
− | |||
===References=== | ===References=== | ||
− | # ''' | + | #'''CONTACT-03:''' Pal SK, Albiges L, Tomczak P, Suárez C, Voss MH, de Velasco G, Chahoud J, Mochalova A, Procopio G, Mahammedi H, Zengerling F, Kim C, Osawa T, Angel M, Gupta S, Khan O, Bergthold G, Liu B, Kalaitzidou M, Huseni M, Scheffold C, Powles T, Choueiri TK. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2023 Jul 15;402(10397):185-195. Epub 2023 Jun 5. [https://doi.org/10.1016/s0140-6736(23)00922-4 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017728/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37290461/ PubMed] [https://clinicaltrials.gov/study/NCT04338269 NCT04338269] |
− | |||
− | |||
==Everolimus monotherapy {{#subobject:893557|Regimen=1}}== | ==Everolimus monotherapy {{#subobject:893557|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | === Regimen {{#subobject:9d436d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ Motzer et al. 2014 (RECORD-3)] | |
− | + | |2009-2011 | |
− | + | | style="background-color:#1a9851" | Randomized Phase 2 (E-switch-ic) | |
− | |||
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− | |||
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− | |[https://www. | ||
− | |style="background-color:#1a9851"|Phase | ||
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|[[#Sunitinib_monotherapy_3|Sunitinib]] | |[[#Sunitinib_monotherapy_3|Sunitinib]] | ||
− | + | | style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS (primary endpoint) | |
− | |style="background-color:#ffffbf"|Inconclusive whether non-inferior | ||
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|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
− | ==== | + | ====Prior treatment criteria==== |
− | *RECORD-3: [[#Sunitinib_monotherapy_2|Sunitinib]] | + | *RECORD-3: [[#Sunitinib_monotherapy_2|Sunitinib]], with progression |
− | ==== | + | </div> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
*[[Everolimus (Afinitor)]] 10 mg PO once per day | *[[Everolimus (Afinitor)]] 10 mg PO once per day | ||
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'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#fff2ae"> | |
− | + | ====Dose and schedule modifications==== | |
− | + | *Everolimus dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability | |
− | + | </div></div> | |
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===References=== | ===References=== | ||
− | # | + | #'''RECORD-3:''' Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. [https://doi.org/10.1200/jco.2013.54.6911 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25049330/ PubMed] [https://clinicaltrials.gov/study/NCT00903175 NCT00903175] |
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==Sorafenib monotherapy {{#subobject:6e18d8|Regimen=1}}== | ==Sorafenib monotherapy {{#subobject:6e18d8|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:a50d71|Variant=1}}=== | ===Regimen {{#subobject:a50d71|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | ! style="width: 20%" |Study |
− | ! | + | ! style="width: 20%" |Dates of enrollment |
− | ![[Levels_of_Evidence# | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! | + | ! style="width: 20%" | Comparator |
− | |Comparator | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | ![[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1002/cncr.24864 Stadler et al. 2010 (ARCCS)] |
− | |style="background-color:# | + | |2005-06 to 2006-07 |
− | | | + | | style="background-color:#91cf61" |Non-randomized expanded access study |
− | + | | style="background-color:#d3d3d3" | | |
− | + | | style="background-color:#d3d3d3" | | |
− | |style="background-color:# | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1093/annonc/mdq651 Beck et al. 2011 (EU-ARCCS)] |
− | + | |2005-2007 | |
− | + | | style="background-color:#91cf61" |Non-randomized expanded access study | |
− | + | | style="background-color:#d3d3d3" | | |
− | + | | style="background-color:#d3d3d3" | | |
− | |||
− | |||
− | |||
− | |style="background-color:#91cf61"|Non-randomized | ||
− | |style="background-color:#d3d3d3"| | ||
− | |style="background-color:#d3d3d3"| | ||
− | |||
− | |||
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|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569683/ Hutson et al. 2013 (INTORSECT)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569683/ Hutson et al. 2013 (INTORSECT)] | ||
− | |style="background-color:#1a9851"|Phase | + | |2007-2011 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |Temsirolimus | + | |[[#Temsirolimus_monotherapy_999|Temsirolimus]] |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<sup>2</sup><br>Median PFS: 3.9 vs 4.3 mo<br>(HR 1.15, 95% CI 0.93-1.41) | |
− | | style="background-color:#ffffbf" | | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for TARGET is based on the 2009 update.''<br> |
− | ==== | + | ''<sup>2</sup>While the primary endpoint (PFS) was not met in INTORSECT, the control arm actually had superior OS compared to the experimental arm.''<br> |
− | *[[Sorafenib (Nexavar)]] 400 mg PO | + | <div class="toccolours" style="background-color:#fdcdac"> |
− | * | + | ====Prior treatment criteria==== |
− | + | *INTORSECT: Sunitinib, with progression | |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
+ | ====Targeted therapy==== | ||
+ | *[[Sorafenib (Nexavar)]] 400 mg PO twice per day | ||
+ | '''Continued indefinitely''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *Sorafenib can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''ARCCS:''' Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Bukowski RM; ARCCS Study Investigators. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. 2010 Mar 1;116(5):1272-80. [https://doi.org/10.1002/cncr.24864 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20082451/ PubMed] [https://clinicaltrials.gov/study/NCT00111020 NCT00111020] | |
− | + | #'''EU-ARCCS:''' Beck J, Procopio G, Bajetta E, Keilholz U, Negrier S, Szczylik C, Bokemeyer C, Bracarda S, Richel DJ, Staehler M, Strauss UP, Mersmann S, Burock K, Escudier B. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann Oncol. 2011 Aug;22(8):1812-23. Epub 2011 Feb 15. [https://doi.org/10.1093/annonc/mdq651 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21324953/ PubMed] | |
− | # '''ARCCS:''' Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Bukowski RM; ARCCS Study Investigators. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. 2010 Mar 1;116(5):1272-80. [https:// | + | #'''INTORSECT:''' Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, Senico P, Niethammer A, Lu DR, Hariharan S, Motzer RJ. Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Mar 10;32(8):760-7. Epub 2013 Dec 2. [https://doi.org/10.1200/JCO.2013.50.3961 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569683/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24297950/ PubMed] [https://clinicaltrials.gov/study/NCT00474786 NCT00474786] |
− | # '''EU-ARCCS:''' Beck J, Procopio G, Bajetta E, Keilholz U, Negrier S, Szczylik C, Bokemeyer C, Bracarda S, Richel DJ, Staehler M, Strauss UP, Mersmann S, Burock K, Escudier B. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann Oncol. 2011 Aug;22(8):1812-23. Epub 2011 Feb 15. [ | ||
− | |||
− | |||
− | # '''INTORSECT:''' Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, Senico P, Niethammer A, Lu DR, Hariharan S, Motzer RJ. Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Mar 10;32(8):760-7. Epub 2013 Dec 2. [ | ||
==Sunitinib monotherapy {{#subobject:f929da|Regimen=1}}== | ==Sunitinib monotherapy {{#subobject:f929da|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:955949|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2005.02.2574 Motzer et al. 2005 (RTKC-0511-014)] |
− | | | + | |2003 |
− | = | + | | style="background-color:#91cf61" |Phase 2 (RT) |
− | + | | style="background-color:#d3d3d3" | | |
− | + | | style="background-color:#d3d3d3" | | |
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|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045%2809%2970162-7 Gore et al. 2009 (A618-1037)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2005-2007 |
− | + | | style="background-color:#91cf61" |Non-randomized | |
− | |style="background-color:#d3d3d3"| | + | | style="background-color:#d3d3d3" | |
− | |style="background-color:#d3d3d3"| | + | | style="background-color:#d3d3d3" | |
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ Motzer et al. 2014 (RECORD-3)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |2009-2011 |
− | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) | |
|[[#Everolimus_monotherapy|Everolimus]] | |[[#Everolimus_monotherapy|Everolimus]] | ||
− | |style="background-color:#ffffbf"|Inconclusive whether non-inferior | + | | style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS (primary endpoint) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *RECORD-3: [[#Everolimus_monotherapy|Everolimus]] | + | *RECORD-3: First-line [[#Everolimus_monotherapy|Everolimus]] |
− | ==== | + | </div> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
*[[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 | ||
− | |||
− | |||
'''42-day cycles''' | '''42-day cycles''' | ||
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#fff2ae"> | |
− | + | ====Dose and schedule modifications==== | |
− | < | + | *Dose may be decreased to 37.5 mg or 25 mg PO once per day depending on tolerability |
− | + | </div></div> | |
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− | ==== | ||
− | * | ||
− | |||
===References=== | ===References=== | ||
− | # Motzer RJ, | + | #'''RTKC-0511-014:''' Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Ginsberg MS, Kim ST, Baum CM, DePrimo SE, Li JZ, Bello CL, Theuer CP, George DJ, Rini BI. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006 Jan 1;24(1):16-24. Epub 2005 Dec 5. [https://doi.org/10.1200/JCO.2005.02.2574 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16330672/ PubMed] |
+ | #'''A618-1037:''' Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schöffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009 Aug;10(8):757-63. Epub 2009 Jul 15. [https://doi.org/10.1016/S1470-2045%2809%2970162-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19615940/ PubMed] [https://clinicaltrials.gov/study/NCT00130897 NCT00130897] | ||
+ | #'''RECORD-3:''' Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. [https://doi.org/10.1200/jco.2013.54.6911 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569681/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25049330/ PubMed] [https://clinicaltrials.gov/study/NCT00903175 NCT00903175] | ||
− | [[Category:Renal | + | [[Category:Renal cell carcinoma regimens]] |
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Genitourinary cancers]] | [[Category:Genitourinary cancers]] |
Latest revision as of 12:46, 23 July 2024
Page editor | Section editor | ||
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Teja Ganta, MD Icahn School of Medicine at Mount Sinai New York, NY, USA |
Ali Raza Khaki, MD Stanford University Palo Alto, CA, USA |
Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page or to a histology- or biomarker-specific page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: This page contains trials that did not specify histology or allowed patients with multiple histologies. Trials limited to a specific histology including those that required a clear-cell component are on dedicated pages:
- Histology-specific:
- Biomarker-specific:
14 regimens on this page
22 variants on this page
|
Living Interactive Systematic Reviews
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ESMO
- 2021: Kanesveran et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma PubMed
- 2021: Powles et al. ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma PubMed
- 2024: Powles et al. Renal cell carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
- 2019: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2016: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2014: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2012: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Escudier & Kataja. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Escudier & Kataja. Renal cell carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
ISRS
- 2024: Siva et al. Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS) PubMed
NCCN
- NCCN Guidelines - Kidney Cancer
- 2022: Motzer et al. Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. link to PMC article PubMed
- 2017: Motzer et al. Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology PubMed
- 2015: Motzer et al. Kidney Cancer, Version 3.2015 PubMed
- 2014: Motzer et al. Kidney cancer, version 2.2014 PubMed
- 2011: Motzer et al. Kidney cancer. PubMed
- 2009: Motzer et al. NCCN clinical practice guidelines in oncology: kidney cancer. PubMed
- 2006: Motzer et al. Kidney cancer. Clinical practice guidelines in oncology. PubMed
- 2005: Motzer et al. Kidney cancer. Clinical practice guidelines. PubMed
SIOG
- 2018: Kanesvaran et al. Elderly patients with metastatic renal cell carcinoma: position paper from the International Society of Geriatric Oncology PubMed
SITC
- 2019: Rini et al. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC) PubMed
Risk Stratification Calculators
- International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) calculator
- ref: Heng DY, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN, Mackenzie M, Wood L, Donskov F, Tan MH, Rha SY, Agarwal N, Kollmannsberger C, Rini BI, Choueiri TK; External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013 Feb;14(2):141-8. Epub 2013 Jan 9. link to PMC article PubMed
- Memorial Sloan Kettering Cancer Center (MSKCC) calculator
- ref: Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002 Jan 1;20(1):289-96. link to original article PubMed
- Mortality and complication risk calculator for a patients with clinical T1 renal cortical mass up to 7 cm (Dr. Sarah P. Psutka)
- ref: Psutka SP et al., A clinical decision aid to support personalized treatment selection for patients with stage T1 renal masses: Results from a multi-institutional competing risks analysis including performance status and comorbidity. Working paper. link to news article
- UCLA Integrated Staging System (UISS) for Renal Cell Carcinoma (RCC)
- ref: Zisman A, Pantuck AJ, Dorey F, Said JW, Shvarts O, Quintana D, Gitlitz BJ, deKernion JB, Figlin RA, Belldegrun AS. Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol. 2001 Mar 15;19(6):1649-57. PubMed
- Leibovich prognostic model
- ref: Leibovich BC, Lohse CM, Cheville JC, Zaid HB, Boorjian SA, Frank I, Thompson RH, Parker WP. Predicting Oncologic Outcomes in Renal Cell Carcinoma After Surgery. Eur Urol. 2018 May;73(5):772-780. Epub 2018 Feb 3. PubMed
Adjuvant therapy
Sunitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Haas et al. 2016 (ECOG-ACRIN E2805) | 2006-2010 | Phase 3 (E-esc) | 1. Placebo 2. Sorafenib |
Did not meet primary endpoint of DFS |
Preceding treatment
Targeted therapy
- Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
42-day cycle for up to 9 cycles (1 year)
References
- ECOG-ACRIN E2805: Haas NB, Manola J, Uzzo RG, Flaherty KT, Wood CG, Kane C, Jewett M, Dutcher JP, Atkins MB, Pins M, Wilding G, Cella D, Wagner L, Matin S, Kuzel TM, Sexton WJ, Wong YN, Choueiri TK, Pili R, Puzanov I, Kohli M, Stadler W, Carducci M, Coomes R, DiPaola RS. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016 May 14;387(10032):2008-16. Epub 2016 Mar 9. Erratum in: Lancet. 2016 May 14;387(10032):1998. link to original article link to PMC article PubMed NCT00326898
Metastatic disease, first-line
Atezolizumab & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rini et al. 2019 (IMmotion151) | 2015-05-20 to 2016-10-12 | Phase 3 (E-esc) | Sunitinib | Seems to have superior PFS1 (co-primary endpoint) Median PFS: 11.2 vs 7.7 mo (HR 0.74, 95% CI 0.57-0.96) |
1Reported efficacy is for the PD-L1-positive subgroup, which was the predefined co-primary endpoint.
Note: patients could have clear cell or sarcomatoid histology.
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- IMmotion151: Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. Epub 2019 May 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02420821
- Update: Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Alekseev BY, Lee JL, Suarez C, Stroyakovskiy D, De Giorgi U, Donskov F, Mellado B, Banchereau R, Hamidi H, Khan O, Craine V, Huseni M, Flinn N, Dubey S, Rini BI. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022 Feb 1;8(2):275-280. link to original article link to PMC article PubMed
Everolimus monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Motzer et al. 2014 (RECORD-3) | 2009-2011 | Randomized Phase 2 (E-switch-ic) | Sunitinib | Inconclusive whether non-inferior PFS (primary endpoint) |
Subsequent treatment
- RECORD-3, upon progression: Second-line Sunitinib
Dose and schedule modifications
- Everolimus dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability
References
- RECORD-3: Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00903175
Gemcitabine & Sunitinib
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Michaelson et al. 2015 (MGH 07-212) | 2007-2013 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 14
21-day cycles
References
- MGH 07-212: Michaelson MD, McKay RR, Werner L, Atkins MB, Van Allen EM, Olivier KM, Song J, Signoretti S, McDermott DF, Choueiri TK. Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Cancer. 2015 Oct 1;121(19):3435-43. Epub 2015 Jun 8. link to original article PubMed NCT00556049
High-dose Interleukin-2
HD IL-2: High-Dose InterLeukin-2
Example orders
Regimen variant #1, 1.8 MU/kg/day, intermittent
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rosenberg et al. 1994 | 1985-1992 | Non-randomized | ||
Fyfe et al. 1995 | Not reported | Phase 2 (RT) | ||
McDermott et al. 2005 | 1997-2000 | Phase 3 (C) | Subcutaneous IL-2 & Interferon | Might have superior PFS |
Immunotherapy
- IL-2 - Aldesleukin (Proleukin) 600,000 units/kg IV every 8 hours for up to 14 doses per week, on days 1 to 5, 15 to 19
Supportive therapy
- Ciprofloxacin (Cipro) 250 mg PO twice per day on days 1 to 10, 15 to 24
- All antihypertensive therapy discontinued at least 24 hours before each cycle
- Acetaminophen (Tylenol) 650 mg PO every 4 hours
- Indomethacin (Indocin) 25 mg PO every 6 hours
- Ranitidine (Zantac) 150 mg PO or Famotidine (Pepcid) 20 mg PO every 12 hours
- Hydroxyzine (Atarax) 25 to 50 mg PO every 6 hours or Diphenhydramine (Benadryl) 25 mg PO every (note: frequency was blank in reference) hours for pruritis
- Meperidine (Demerol) 25 to 50 mg PO every 6 hours for chills and rigors
- "An antidiarrheal agent, antiemetics, anxiolytics, diuretics, and vasopressors as needed"
28-day cycle for up to 3 cycles
Regimen variant #2, 2.16 MU/kg/day, intermittent, goal 10.8 MU
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yang et al. 1994 | 1991-1993 | Phase 3 (C) | 1. LD IL-2 (IV) | Seems to have superior ORR |
2. LD IL-2 (SC) | Seems to have superior ORR |
Note: reported efficacy is based on the 2003 update.
Immunotherapy
- IL-2 - Aldesleukin (Proleukin) 720,000 units/kg IV every 8 hours for up to 15 doses
- Then after 7 to 10 days of rest, IL-2 - Aldesleukin (Proleukin) 720,000 units/kg IV every 8 hours for up to 15 doses is given again
8-week cycle for up to 2 cycles
Regimen variant #3, 5 MU/m2/day, CI
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Figlin et al. 1999 | 1994-1997 | Phase 3 (C) | IL-2 & CD8+ TILs | Did not meet primary endpoint of ORR |
Immunotherapy
- IL-2 - Aldesleukin (Proleukin) 5,000,000 units/m2/day IV continuous infusion over 96 hours, started on days 1, 8, 15, 22 (total dose per cycle: 80 MU/m2)
8-week cycles
References
- Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994 Mar 23-30;271(12):907-13. link to original article PubMed
- Yang JC, Topalian SL, Parkinson D, Schwartzentruber DJ, Weber JS, Ettinghausen SE, White DE, Steinberg SM, Cole DJ, Kim HI, Levin R, Guleria A, MacFarlane MP, White RL, Einhorn JH, Seipp CA, Rosenberg SA. Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J Clin Oncol. 1994 Aug;12(8):1572-6. link to original article PubMed
- Update: Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003 Aug 15;21(16):3127-32. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995 Mar;13(3):688-96. link to original article PubMed
- Figlin RA, Thompson JA, Bukowski RM, Vogelzang NJ, Novick AC, Lange P, Steinberg GD, Belldegrun AS. Multicenter, randomized, phase III trial of CD8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol. 1999 Aug;17(8):2521-9. link to original article dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed
Low-dose Interleukin-2
LD IL-2: Low-Dose InterLeukin-2
Regimen variant #1, Intravenous
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yang et al. 1994 | 1991-1993 | Phase 3 (E-de-esc) | 1. High-dose IL-2 | Seems to have inferior ORR |
2. LD IL-2; SC | Not reported |
Note: efficacy is based on the 2003 update.
Immunotherapy
- IL-2 - Aldesleukin (Proleukin) as follows:
- Week 1: 72,000 units/kg IV every 8 hours for up to 15 doses
- Then after 7 to 10 days of rest: 72,000 units/kg IV every 8 hours for up to 15 doses is given again
8-week cycle for up to 2 cycles
Regimen variant #2, Subcutaneous
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yang et al. 1994 | 1991-1993 | Phase 3 (E-de-esc) | 1. High-dose IL-2 | Seems to have inferior ORR |
2. LD IL-2; IV | Not reported |
Note: this arm was added to the trial after the interim results were announced in 1994.
Immunotherapy
- IL-2 - Aldesleukin (Proleukin) as follows:
- Week 1: 250,000 units/kg SC once per day for 5 days
- Weeks 2 to 6: 125,000 units/kg SC once per day for 5 days per week
8-week cycle for up to 2 cycles
References
- Yang JC, Topalian SL, Parkinson D, Schwartzentruber DJ, Weber JS, Ettinghausen SE, White DE, Steinberg SM, Cole DJ, Kim HI, Levin R, Guleria A, MacFarlane MP, White RL, Einhorn JH, Seipp CA, Rosenberg SA. Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J Clin Oncol. 1994 Aug;12(8):1572-6. link to original article PubMed
- Update: Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003 Aug 15;21(16):3127-32. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
Interferon alfa-2a monotherapy
Regimen variant #1, 5 MU 5x per week
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sagaster et al. 1995 | Not reported-1992 | Phase 3 (C) | Cimetidine, Coumarin, IFN alfa-2a | Did not meet primary endpoint of ORR |
Immunotherapy
- Interferon alfa-2a (Roferon-A) 5,000,000 units SC once per day on days 1 to 5 (5 times per week)
7-day cycles
Regimen variant #2, 9 MU TIW
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gore et al. 2010 (MRC RE04/EORTC GU 30012) | 2001-2006 | Phase 3 (C) | 5-FU, Interferon alfa-2a, IL-2 | Did not meet primary endpoint of OS |
Hawkins et al. 2016 (Active Biotech 06762004) | 2007-2010 | Phase 2/3 (C) | Naptumomab estafenatox + IFNα | Did not meet primary endpoint of OS |
Immunotherapy
- Interferon alfa-2a (Roferon-A) 9,000,000 units SC 3 times per week
Given for varying lengths of time; see individual trials
Dose and schedule modifications
- Some protocols: Dose can be reduced to 3,000,000 or 6,000,000 units SC 3 times per week based on tolerability
Regimen variant #3, 9 MU daily, with lead-in
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Motzer et al. 2000 | 1994-1996 | Phase 3 (C) | IFN alfa & 13-CRA | Did not meet primary endpoint of ORR |
Note: Interferon alfa-2a dose was increased only if the prior dose was tolerated.
Immunotherapy
- Interferon alfa-2a (Roferon-A) as follows:
- Cycle 1: 3,000,000 units SC once per day on days 1 to 7
- Cycle 2: 6,000,000 units SC once per day on days 1 to 7
- Cycle 3 onwards: 9,000,000 units SC once per day on days 1 to 7
7-day cycles
Regimen variant #4, 10 MU TIW, with lead-in
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ritchie et al. 1999 (MRC RE01) | 1992-1997 | Phase 3 (E-switch-ooc) | MPA | Superior OS (primary endpoint) Median OS: 8.5 vs 6 mo (HR 0.72, 95% CI 0.55-0.94) |
Immunotherapy
- Interferon alfa-2a (Roferon-A) as follows:
- Cycle 1: 5,000,000 units SC once per day on days 1 & 3, then 10,000,000 units SC once on day 5
- Cycles 2 to 12: 10,000,000 units SC once per day on days 1, 3, 5 (3 times per week)
7-day cycle for 12 cycles
Regimen variant #5, 10 MU TIW
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gore et al. 2010 (MRC RE04/EORTC GU 30012) | 2001-2006 | Phase 3 (C) | 5-FU, Interferon alfa-2a, IL-2 | Did not meet primary endpoint of OS |
Immunotherapy
- Interferon alfa-2a (Roferon-A) 10,000,000 units SC once per day on days 1, 3, 5 (3 times per week)
7-day cycles
Regimen variant #6, 18 MU TIW, with lead-in
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fosså et al. 1992 | 1985-1986 | Phase 3 (C) | IFN alfa-2a & Vinblastine | Did not meet efficacy endpoints |
Hudes et al. 2007 (ARCC) | 2003-2005 | Phase 3 (C) | 1. Interferon alfa-2a & Temsirolimus | Did not meet primary endpoint of OS |
2. Temsirolimus | Inferior OS |
Note: Interferon alfa-2a dose was increased only if the prior dose was tolerated.
Immunotherapy
- Interferon alfa-2a (Roferon-A) as follows:
- Cycle 1: 3,000,000 units SC once per day on days 1, 3, 5
- Cycle 2: 9,000,000 units SC once per day on days 1, 3, 5
- Cycle 3 onwards: 18,000,000 units SC once per day on days 1, 3, 5
7-day cycles
Dose and schedule modifications
- If higher doses cannot be tolerated, highest tolerable doses of 3,000,000, 4,500,500, or 6,000,000 units can be used
References
- Fosså SD, Martinelli G, Otto U, Schneider G, Wander H, Oberling F, Bauer HW, Achtnicht U, Holdener EE. Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study. Ann Oncol. 1992 Apr;3(4):301-5. link to original article PubMed
- Sagaster P, Micksche M, Flamm J, Ludwig H. Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer. Ann Oncol. 1995 Dec;6(10):999-1003. link to original article dosing details in abstract have been reviewed by our editors PubMed
- MRC RE01: Ritchie A, Griffiths G, Parmar M; Medical Research Council Renal Cancer Collaborators. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Lancet. 1999 Jan 2;353(9146):14-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Motzer RJ, Murphy BA, Bacik J, Schwartz LH, Nanus DM, Mariani T, Loehrer P, Wilding G, Fairclough DL, Cella D, Mazumdar M. Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol. 2000 Aug;18(16):2972-80. link to original article PubMed
- ARCC: Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00065468
- MRC RE04/EORTC GU 30012: Gore ME, Griffin CL, Hancock B, Patel PM, Pyle L, Aitchison M, James N, Oliver RT, Mardiak J, Hussain T, Sylvester R, Parmar MK, Royston P, Mulders PF. Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial. Lancet. 2010 Feb 20;375(9715):641-8. Epub 2010 Feb 10. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00053820
- Active Biotech 06762004: Hawkins RE, Gore M, Shparyk Y, Bondar V, Gladkov O, Ganev T, Harza M, Polenkov S, Bondarenko I, Karlov P, Karyakin O, Khasanov R, Hedlund G, Forsberg G, Nordle Ö, Eisen T. A randomized phase II/III study of naptumomab estafenatox + IFNα versus IFNα in renal cell carcinoma: final analysis with baseline biomarker subgroup and trend analysis. Clin Cancer Res. 2016 Jul 1;22(13):3172-81. Epub 2016 Feb 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00420888
Sorafenib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stadler et al. 2010 (ARCCS) | 2005-06 to 2006-07 | Non-randomized | ||
Retz et al. 2018 (SWITCH-II) | 2012-06-14 to 2016-11-14 | Phase 3 (C) | Pazopanib | Inconclusive whether non-inferior tPFS |
Dose and schedule modifications
- Sorafenib can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity
Subsequent treatment
- SWITCH-II, upon progression: Pazopanib
References
- ARCCS: Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Bukowski RM; ARCCS Study Investigators. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. 2010 Mar 1;116(5):1272-80. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00111020
- SWITCH-II: Retz M, Bedke J, Bögemann M, Grimm MO, Zimmermann U, Müller L, Leiber C, Teber D, Wirth M, Bolenz C, van Alphen R, De Santis M, Beeker A, Lehmann J, Indorf M, Frank M, Bokemeyer C, Gschwend JE. SWITCH II: Phase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of advanced or metastatic renal cell carcinoma (AUO AN 33/11). Eur J Cancer. 2019 Jan;107:37-45. Epub 2018 Dec 7. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01613846
Sunitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gore et al. 2009 (A618-1037) | 2005-2007 | Non-randomized | ||
Motzer et al. 2014 (RECORD-3) | 2009-2011 | Randomized Phase 2 (E-switch-ic) | Everolimus | Inconclusive whether non-inferior PFS (primary endpoint) |
Eichelberg et al. 2015 (SWITCH) | 2009-2011 | Phase 3 (C) | Sorafenib | Did not meet primary endpoint of PFS |
Rini et al. 2019 (IMmotion151) | 2015-05-20 to 2016-10-12 | Phase 3 (C) | Atezolizumab & Bevacizumab | Seems to have inferior PFS |
Subsequent treatment
- SWITCH, upon progression: Second-line Sorafenib
Dose and schedule modifications
- Per some references, dose may be decreased to 37.5 mg or 25 mg PO once per day depending on tolerability
References
- A618-1037: Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schöffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009 Aug;10(8):757-63. Epub 2009 Jul 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00130897
- PISCES: Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, Gschwend JE, De Giorgi U, Parikh O, Hawkins R, Sevin E, Négrier S, Khan S, Diaz J, Redhu S, Mehmud F, Cella D. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014 May 10;32(14):1412-8. Epub 2014 Mar 31. link to original article PubMed NCT01064310
- RECORD-3: Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00903175
- SWITCH: Eichelberg C, Vervenne WL, De Santis M, Fischer von Weikersthal L, Goebell PJ, Lerchenmüller C, Zimmermann U, Bos MM, Freier W, Schirrmacher-Memmel S, Staehler M, Pahernik S, Los M, Schenck M, Flörcken A, van Arkel C, Hauswald K, Indorf M, Gottstein D, Michel MS. SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer. Eur Urol. 2015 Nov;68(5):837-47. Epub 2015 May 4. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00732914
- IMmotion151: Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. Epub 2019 May 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02420821
- Update: Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Alekseev BY, Lee JL, Suarez C, Stroyakovskiy D, De Giorgi U, Donskov F, Mellado B, Banchereau R, Hamidi H, Khan O, Craine V, Huseni M, Flinn N, Dubey S, Rini BI. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022 Feb 1;8(2):275-280. link to original article link to PMC article PubMed
Temsirolimus monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hudes et al. 2007 (ARCC) | 2003-2005 | Phase 3 (E-RT-switch-ooc) | 1. Interferon alfa-2a | Superior OS (primary endpoint) Median OS: 10.9 vs 7.3 mo (HR 0.73, 95% CI 0.58-0.92) |
2. Interferon alfa-2a & Temsirolimus | Not reported |
Targeted therapy
- Temsirolimus (Torisel) 25 mg IV over 30 minutes once on day 1
Supportive therapy
- Diphenhydramine (Benadryl) (or similar H1 blocker) 25 to 50 mg IV once on day 1; 30 minutes prior to temsirolimus
7-day cycles
References
- ARCC: Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00065468
Metastatic disease, second-line
Cabozantinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pal et al. 2023 (CONTACT-03) | 2020-07-28 to 2021-12-27 | Phase 3 (C) | Cabozantinib & Atezolizumab | Did not meet co-primary endpoints of PFS/OS |
Targeted therapy
- Cabozantinib (Cabometyx) 60 mg PO once per day on days 1 to 28, taken at least 2 hours before or 1 hour after meals
28-day cycles
References
- CONTACT-03: Pal SK, Albiges L, Tomczak P, Suárez C, Voss MH, de Velasco G, Chahoud J, Mochalova A, Procopio G, Mahammedi H, Zengerling F, Kim C, Osawa T, Angel M, Gupta S, Khan O, Bergthold G, Liu B, Kalaitzidou M, Huseni M, Scheffold C, Powles T, Choueiri TK. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2023 Jul 15;402(10397):185-195. Epub 2023 Jun 5. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT04338269
Everolimus monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Motzer et al. 2014 (RECORD-3) | 2009-2011 | Randomized Phase 2 (E-switch-ic) | Sunitinib | Inconclusive whether non-inferior PFS (primary endpoint) |
Prior treatment criteria
- RECORD-3: Sunitinib, with progression
Dose and schedule modifications
- Everolimus dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability
References
- RECORD-3: Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00903175
Sorafenib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stadler et al. 2010 (ARCCS) | 2005-06 to 2006-07 | Non-randomized expanded access study | ||
Beck et al. 2011 (EU-ARCCS) | 2005-2007 | Non-randomized expanded access study | ||
Hutson et al. 2013 (INTORSECT) | 2007-2011 | Phase 3 (C) | Temsirolimus | Did not meet primary endpoint of PFS2 Median PFS: 3.9 vs 4.3 mo (HR 1.15, 95% CI 0.93-1.41) |
1Reported efficacy for TARGET is based on the 2009 update.
2While the primary endpoint (PFS) was not met in INTORSECT, the control arm actually had superior OS compared to the experimental arm.
Prior treatment criteria
- INTORSECT: Sunitinib, with progression
Dose and schedule modifications
- Sorafenib can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity
References
- ARCCS: Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Bukowski RM; ARCCS Study Investigators. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. 2010 Mar 1;116(5):1272-80. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00111020
- EU-ARCCS: Beck J, Procopio G, Bajetta E, Keilholz U, Negrier S, Szczylik C, Bokemeyer C, Bracarda S, Richel DJ, Staehler M, Strauss UP, Mersmann S, Burock K, Escudier B. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann Oncol. 2011 Aug;22(8):1812-23. Epub 2011 Feb 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- INTORSECT: Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, Senico P, Niethammer A, Lu DR, Hariharan S, Motzer RJ. Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Mar 10;32(8):760-7. Epub 2013 Dec 2. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT00474786
Sunitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Motzer et al. 2005 (RTKC-0511-014) | 2003 | Phase 2 (RT) | ||
Gore et al. 2009 (A618-1037) | 2005-2007 | Non-randomized | ||
Motzer et al. 2014 (RECORD-3) | 2009-2011 | Randomized Phase 2 (E-switch-ic) | Everolimus | Inconclusive whether non-inferior PFS (primary endpoint) |
Preceding treatment
- RECORD-3: First-line Everolimus
Dose and schedule modifications
- Dose may be decreased to 37.5 mg or 25 mg PO once per day depending on tolerability
References
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