Urothelial carcinoma - null regimens

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 DFS Median DFS: 16.6 vs 19.4 mo (HR 1.12, 95% CI 0.93-1.35)

Preceding treatment

• Radical cystectomy or nephroureterectomy with lymph node dissection

References

1. 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 PubMed NCT02450331

Placebo

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Bajorin et al. 2021 (CheckMate 274)	2016-2020	Phase 3 (C)	Nivolumab	Inferior DFS

No active antineoplastic therapy.

Preceding treatment

• Radical surgery

References

1. 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 PubMed NCT02632409
   1. 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 PubMed

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	Inferior 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

1. 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 PubMed NCT02603432
   1. 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 PubMed
   2. 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 PubMed

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	Inferior OS1

¹Reported efficacy is based on the 2013 update.
No active antineoplastic treatment.

References

1. 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 PubMed NCT00315237
   1. 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 PubMed