Latest revision as of 12:41, 10 June 2024

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main clear cell RCC page for regimens that include active anticancer treatment.

Adjuvant therapy

Placebo

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Ravaud et al. 2016 (S-TRAC)	2007-2011	Phase 3 (C)	Sunitinib	Seems to have inferior DFS	Less toxicity
Choueiri et al. 2021 (KEYNOTE-564)	2017-2019	Phase 3 (C)	Pembrolizumab	Inferior OS¹
Motzer et al. 2023 (CheckMate 914 part A)	2017-08-28 to 2021-03-16	Phase 3 (C)	Ipilimumab & Nivolumab	Did not meet primary endpoint of DFS

¹Reported efficacy for KEYNOTE-564 is based on the 2024 update.
No active antineoplastic treatment.

Preceding treatment

Surgery

References

S-TRAC: Ravaud A, Motzer RJ, Pandha HS, George DJ, Pantuck AJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Martini JF, Ramaswamy K, Casey M, Staehler M, Patard JJ; S-TRAC Investigators. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. 2016 Dec 8;375(23):2246-2254. Epub 2016 Oct 9. link to original article PubMed NCT00375674
1. Update: Motzer RJ, Ravaud A, Patard JJ, Pandha HS, George DJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Casey M, Serfass L, Pantuck AJ, Staehler M. Adjuvant sunitinib for high-risk renal cell carcinoma after nephrectomy: subgroup analyses and updated overall survival results. Eur Urol. 2018 Jan;73(1):62-68. Epub 2017 Sep 26. link to original article link to PMC article PubMed
KEYNOTE-564: Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, Hajek J, Symeonides SN, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Gurney H, Chevreau C, Melichar B, Kopyltsov E, Alva A, Burke JM, Doshi G, Topart D, Oudard S, Hammers H, Kitamura H, Bedke J, Perini RF, Zhang P, Imai K, Willemann-Rogerio J, Quinn DI, Powles T; KEYNOTE-564 Investigators. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med. 2021 Aug 19;385(8):683-694. link to original article PubMed NCT03142334
1. Update: Powles T, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Gurney H, Chang YH, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Burgents JE, Xu L, Imai K, Quinn DI, Choueiri TK; KEYNOTE-564 Investigators. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Sep;23(9):1133-1144. link to original article PubMed
2. Update: Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Chang YH, Lee JL, Sarwar N, Haas NB, Gurney H, Sawrycki P, Mahave M, Gross-Goupil M, Zhang T, Burke JM, Doshi G, Melichar B, Kopyltsov E, Alva A, Oudard S, Topart D, Hammers H, Kitamura H, McDermott DF, Silva A, Winquist E, Cornell J, Elfiky A, Burgents JE, Perini RF, Powles T; KEYNOTE-564 Investigators. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med. 2024 Apr 18;390(15):1359-1371. link to original article PubMed
CheckMate 914 part A: Motzer RJ, Russo P, Gruenwald V, Tomita Y, Zurawski B, Parikh O, Buti S, Barthelemy P, Goh JC, Ye D, Lingua A, Lattouf JB, Albiges L, George S, Shuch B, Sosman J, Staehler M, Vazquez Estevez S, Simsek B, Spiridigliozzi J, Chudnovsky A, Bex A. Adjuvant nivolumab plus ipilimumab versus placebo for localised renal cell carcinoma after nephrectomy (CheckMate 914): a double-blind, randomised, phase 3 trial. Lancet. 2023 Mar 11;401(10379):821-832. Epub 2023 Feb 9. link to original article PubMed NCT03138512

Metastatic disease, first-line

Placebo

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sternberg et al. 2010 (VEG105192)	2006-04 to 2007-04	Phase 3 (C)	Pazopanib	Inferior PFS

No active antineoplastic treatment.

References

VEG105192: Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. Epub 2010 Jan 25. link to original article PubMed NCT00334282
1. Update: Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013 Apr;49(6):1287-96. Epub 2013 Jan 12. link to original article PubMed

Metastatic disease, second-line

Placebo

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Yang et al. 2003	1998-2001	Randomized Phase 2 (C)	Bevacizumab	Inferior TTP
Escudier et al. 2007 (TARGET_RCC)	2003-2005	Phase 3 (C)	Sorafenib	Might have inferior OS¹
Motzer et al. 2008 (RECORD-1)	2006-04 to 2007-04	Phase 3 (C)	Everolimus	Inferior PFS

¹Reported efficacy for TARGET is based on the 2009 update.
No active antineoplastic treatment. Note that TARGET should not be confused with the study by the same name in breast cancer.

Prior treatment criteria

Yang et al. 2003: Previous therapy with IL-2 or contraindication to IL-2
RECORD-1: Progression on sunitinib, sorafenib, or both
TARGET_RCC: Progression after 1 systemic treatment within the previous 8 months

References

Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003 Jul 31;349(5):427-34. link to original article link to PMC article PubMed
RECORD-1: Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. Epub 2008 Jul 22. link to original article PubMed NCT00410124
1. Update: Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer. 2010 Sep 15;116(18):4256-65. link to original article PubMed
TARGET_RCC: Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. Erratum in: N Engl J Med. 2007 Jul 12;357(2):203. link to original article PubMed NCT00073307
1. Update: Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, Negrier S, Chevreau C, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Anderson S, Hofilena G, Shan M, Pena C, Lathia C, Bukowski RM. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009 Jul 10;27(20):3312-8. Epub 2009 May 18. link to original article PubMed
2. Subgroup analysis: Hutson TE, Bellmunt J, Porta C, Szczylik C, Staehler M, Nadel A, Anderson S, Bukowski R, Eisen T, Escudier B; Sorafenib TARGET Clinical Trial Group. Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. Eur J Cancer. 2010 Sep;46(13):2432-40. Epub 2010 Jul 23. link to original article PubMed

@@ Line 10: / Line 10: @@
 <div class="toccolours" style="background-color:#eeeeee">
 ===Regimen===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 17%"|Study
-!style="width: 20%"|Dates of enrollment
+!style="width: 15%"|Dates of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+!style="width: 17%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|[https://doi.org/10.1056/NEJMoa1611406 Ravaud et al. 2016 (S-TRAC)]
+|2007-2011
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Renal_cell_carcinoma#Sunitinib_monotherapy|Sunitinib]]
+| style="background-color:#fc8d59" |Seems to have inferior DFS
+| style="background-color:#1a9850" |Less toxicity
 |-
 |[https://doi.org/10.1056/nejmoa2106391 Choueiri et al. 2021 (KEYNOTE-564)]
@@ Line 22: / Line 30: @@
 |[[Clear_cell_renal_cell_carcinoma#Pembrolizumab_monotherapy|Pembrolizumab]]
 | style="background-color:#d73027" |Inferior OS<sup>1</sup>
+|
 |-
 |[https://doi.org/10.1016/S0140-6736(22)02574-0 Motzer et al. 2023 (CheckMate 914 part A)]
@@ Line 28: / Line 37: @@
 |[[#Ipilimumab_.26_Nivolumab_999|Ipilimumab & Nivolumab]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
+|
 |-
 |}
-''<sup>1</sup>Reported efficacy for KEYTNOTE-564 is based on the 2024 update.''<br>
+''<sup>1</sup>Reported efficacy for KEYNOTE-564 is based on the 2024 update.''<br>
 ''No active antineoplastic treatment.''
 <div class="toccolours" style="background-color:#cbd5e8">
@@ Line 37: / Line 47: @@
 </div></div>
 ===References===
+# '''S-TRAC:''' Ravaud A, Motzer RJ, Pandha HS, George DJ, Pantuck AJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Martini JF, Ramaswamy K, Casey M, Staehler M, Patard JJ; S-TRAC Investigators. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. 2016 Dec 8;375(23):2246-2254. Epub 2016 Oct 9. [https://doi.org/10.1056/NEJMoa1611406 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27718781/ PubMed] [https://clinicaltrials.gov/study/NCT00375674 NCT00375674]
+## '''Update:''' Motzer RJ, Ravaud A, Patard JJ, Pandha HS, George DJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Casey M, Serfass L, Pantuck AJ, Staehler M. Adjuvant sunitinib for high-risk renal cell carcinoma after nephrectomy: subgroup analyses and updated overall survival results. Eur Urol. 2018 Jan;73(1):62-68. Epub 2017 Sep 26. [https://doi.org/10.1016/j.eururo.2017.09.008 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6684251/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28967554/ PubMed]
 # '''KEYNOTE-564:''' Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, Hajek J, Symeonides SN, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Gurney H, Chevreau C, Melichar B, Kopyltsov E, Alva A, Burke JM, Doshi G, Topart D, Oudard S, Hammers H, Kitamura H, Bedke J, Perini RF, Zhang P, Imai K, Willemann-Rogerio J, Quinn DI, Powles T; KEYNOTE-564 Investigators. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med. 2021 Aug 19;385(8):683-694. [https://doi.org/10.1056/nejmoa2106391 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34407342/ PubMed] [https://clinicaltrials.gov/study/NCT03142334 NCT03142334]
 ##'''Update:''' Powles T, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Gurney H, Chang YH, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Burgents JE, Xu L, Imai K, Quinn DI, Choueiri TK; KEYNOTE-564 Investigators. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Sep;23(9):1133-1144. [https://doi.org/10.1016/s1470-2045(22)00487-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36055304/ PubMed]

Difference between revisions of "Clear cell renal cell carcinoma - null regimens"

Latest revision as of 12:41, 10 June 2024

Contents

Adjuvant therapy

Placebo

Regimen

Preceding treatment

References

Metastatic disease, first-line

Placebo

Regimen

References

Metastatic disease, second-line

Placebo

Regimen

Prior treatment criteria

References

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