Clear cell renal cell carcinoma - null regimens

The purpose of this page is to provide references to "null therapy" such as placebo and observation. While not clinically relevant, these references provide further insight into the historical development of the treatment landscape. See the main clear cell RCC page for current regimens.

Adjuvant therapy

Placebo

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Choueiri et al. 2021 (KEYNOTE-564)	2017-2019	Phase 3 (C)	Pembrolizumab	Inferior DFS
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

No active antineoplastic treatment.

Preceding treatment

• Surgery

References

1. 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 contains dosing details in manuscript PubMed Clinical Trial Registry
   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. 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 Clinical Trial Registry

Metastatic disease, second-line

Placebo

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Escudier et al. 2007 (TARGETRCC)	2003-2005	Phase 3 (C)	Sorafenib	Might have inferior OS1

No active antineoplastic treatment. Note that TARGET should not be confused with the study by the same name in breast cancer.

Prior treatment criteria

• TARGET_RCC: Progression after 1 systemic treatment within the previous 8 months

References

1. 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 contains dosing details in manuscript PubMed Clinical Trial Registry
   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 contains dosing details in manuscript PubMed