Urothelial carcinoma - null regimens

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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 urothelial carcinoma page for regimens that include active anticancer treatment.
=Adjuvant chemotherapy=
==Observation==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Bellmunt et al. 2021 (IMvigor010)	2015-2018 	Phase 3 (C)	Atezolizumab 	Did not meet primary endpoint of DFSMedian DFS: 16.6 vs 19.4 mo(HR 1.12, 95% CI 0.93-1.35)
Apolo et al. 2024 (AMBASSADOR) 	2017-09-21 to 2021-08-24	Phase 3 (C)	Pembrolizumab	Shorter DFS (co-primary endpoint)Median DFS: 14.2 vs 29.6 mo(HR 1.37, 95% CI 1.11-1.69)
====Preceding treatment====
*Radical cystectomy or nephroureterectomy with lymph node dissection
===References===
#IMvigor010: Bellmunt J, Hussain M, Gschwend JE, Albers P, Oudard S, Castellano D, Daneshmand S, Nishiyama H, Majchrowicz M, Degaonkar V, Shi Y, Mariathasan S, Grivas P, Drakaki A, O'Donnell PH, Rosenberg JE, Geynisman DM, Petrylak DP, Hoffman-Censits J, Bedke J, Kalebasty AR, Zakharia Y, van der Heijden MS, Sternberg CN, Davarpanah NN, Powles T; IMvigor010 Study Group. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):525-537. Epub 2021 Mar 12. link to original article link to PMC article EuroPMC NCT02450331
# AMBASSADOR: Apolo AB, Ballman KV, Sonpavde G, Berg S, Kim WY, Parikh R, Teo MY, Sweis RF, Geynisman DM, Grivas P, Chatta G, Reichert ZR, Kim JW, Bilen MA, McGregor B, Singh P, Tripathi A, Cole S, Simon N, Niglio S, Ley L, Cordes L, Srinivas S, Huang J, Odegaard M, Watt C, Petrylak D, Hoffman-Censits J, Wen Y, Hahn O, Mitchell C, Tan A, Streicher H, Sharon E, Moon H, Woods M, Halabi S, Perez Burbano G, Morris MJ, Rosenberg JE. Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2025 Jan 2;392(1):45-55. Epub 2024 Sep 15. link to original article link to PMC article EuroPMC NCT03244384
==Placebo==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Bajorin et al. 2021 (CheckMate 274)	2016-2020 	Phase 3 (C)	Nivolumab 	Shorter DFSMedian DFS: 10.8 vs 20.8 mo(HR 1.43, 98.22% CI 1.11-1.82)
No active antineoplastic therapy.
====Preceding treatment====
*Radical surgery
===References===
#CheckMate 274: Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Ye D, Agerbaek M, Enting D, McDermott R, Gajate P, Peer A, Milowsky MI, Nosov A, Neif Antonio J Jr, Tupikowski K, Toms L, Fischer BS, Qureshi A, Collette S, Unsal-Kacmaz K, Broughton E, Zardavas D, Koon HB, Galsky MD. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021 Jun 3;384(22):2102-2114. link to original article link to PMC article EuroPMC NCT02632409
##HRQoL analysis: Witjes JA, Galsky MD, Gschwend JE, Broughton E, Braverman J, Nasroulah F, Maira-Arce M, Ye X, Shi L, Guo S, Hamilton M, Bajorin DF. Health-related Quality of Life with Adjuvant Nivolumab After Radical Resection for High-risk Muscle-invasive Urothelial Carcinoma: Results from the Phase 3 CheckMate 274 Trial. Eur Urol Oncol. 2022 Oct;5(5):553-563. Epub 2022 Mar 11. link to original article link to PMC article EuroPMC
##Update: Galsky MD, Witjes JA, Gschwend JE, Milowsky MI, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Agerbaek M, Jha G, Stenner F, Ye D, Giudici F, Dutta S, Askelson M, Nasroulah F, Zhang J, Brophy L, Bajorin DF. Adjuvant Nivolumab in High-Risk Muscle-Invasive Urothelial Carcinoma: Expanded Efficacy From CheckMate 274. J Clin Oncol. 2025 Jan;43(1):15-21. Epub 2024 Oct 11. link to original article EuroPMC
=Maintenance after first-line therapy=
==Best supportive care==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy	Comparative Toxicity
Powles et al. 2020 (JAVELIN Bladder 100)	2016-2019 	Phase 3 (C)	Avelumab 	Shorter OS 	Less toxic
No further active antineoplastic treatment.
====Preceding treatment====
*First-line GC x 4 to 6 or GCb x 4 to 6 cycles
===References===
#JAVELIN Bladder 100: Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulović S, Demey W, Ullén A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. Epub 2020 Sep 18. link to original article EuroPMC NCT02603432
##PRO analysis: Grivas P, Kopyltsov E, Su PJ, Parnis FX, Park SH, Yamamoto Y, Fong PC, Tournigand C, Climent Duran MA, Bamias A, Caserta C, Chang J, Cislo P, di Pietro A, Wang J, Powles T. Patient-reported Outcomes from JAVELIN Bladder 100: Avelumab First-line Maintenance Plus Best Supportive Care Versus Best Supportive Care Alone for Advanced Urothelial Carcinoma. Eur Urol. 2023 Apr;83(4):320-328. Epub 2022 May 30. link to original article EuroPMC
##Update: Powles T, Park SH, Caserta C, Valderrama BP, Gurney H, Ullén A, Loriot Y, Sridhar SS, Sternberg CN, Bellmunt J, Aragon-Ching JB, Wang J, Huang B, Laliberte RJ, di Pietro A, Grivas P. Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After ≥2 Years of Follow-Up. J Clin Oncol. 2023 Jul 1;41(19):3486-3492. Epub 2023 Apr 18. link to original article link to PMC article EuroPMC
==Placebo==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Galsky et al. 2020 (HCRN GU14-182)	2015-2018 	Randomized Phase 2 (C)	Pembrolizumab	Seems to have shorter PFS (primary endpoint)Median PFS: 3 vs 5.4 mo(HR 1.54, 95% CI 1.03-2.33)	Less toxic
====Preceding treatment====
*First-line platinum-based combination chemotherapy for up to 8 cycles, without progression of disease
===References===
#HCRN GU14-182: Galsky MD, Mortazavi A, Milowsky MI, George S, Gupta S, Fleming MT, Dang LH, Geynisman DM, Walling R, Alter RS, Kassar M, Wang J, Gupta S, Davis N, Picus J, Philips G, Quinn DI, Haines GK 3rd, Hahn NM, Zhao Q, Yu M, Pal SK. Randomized Double-Blind Phase II Study of Maintenance Pembrolizumab Versus Placebo After First-Line Chemotherapy in Patients With Metastatic Urothelial Cancer. J Clin Oncol. 2020 Jun 1;38(16):1797-1806. Epub 2020 Apr 9. link to original article link to PMC article EuroPMC NCT02500121
=Locally advanced or metastatic disease, subsequent lines=
==Best supportive care==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Bellmunt et al. 2009 (CA183004)	2003-2006 	Phase 3 (C)	Vinflunine	Shorter OS1
1Reported efficacy is based on the 2013 update.
No active antineoplastic treatment.
===References===
#CA183004: Bellmunt J, Théodore C, Demkov T, Komyakov B, Sengelov L, Daugaard G, Caty A, Carles J, Jagiello-Gruszfeld A, Karyakin O, Delgado FM, Hurteloup P, Winquist E, Morsli N, Salhi Y, Culine S, von der Maase H. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009 Sep 20;27(27):4454-61. Epub 2009 Aug 17. Erratum in: J Clin Oncol. 2010 Jan 1;28(1):182. Winquist, Eric [added]. link to original article EuroPMC NCT00315237
##Update: Bellmunt J, Fougeray R, Rosenberg JE, von der Maase H, Schutz FA, Salhi Y, Culine S, Choueiri TK. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Ann Oncol. 2013 Jun;24(6):1466-72. Epub 2013 Feb 17. link to original article EuroPMC
Category:Urothelial carcinoma regimens
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Category:Genitourinary cancers
Category:Null regimens