A Study of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel, or Vinflunine for Participants With Advanced Urothelial Cancer (MK-3475-045/KEYNOTE-045)

Summary

Participants with metastatic or locally advanced/unresectable urothelial cancer that has recurred or progressed following platinum-based chemotherapy will be randomly assigned to receive Investigator's choice of paclitaxel, docetaxel, or vinflunine (Control), or pembrolizumab. The primary study hypotheses are that pembrolizumab will prolong Overall Survival (OS) and Progression-free Survival (PFS) compared to paclitaxel, docetaxel, or vinflunine.

Timeline

Start

2014-10-22

Primary completion

2016-09-07

Completion

2020-10-01

Outcome

Mixed primary results

paper There was no significant between-group difference in the duration of progression-free survival in the total population PMID 28212060 ↗

paper Pembrolizumab was associated with significantly longer overall survival PMID 28212060 ↗

registry analysis (unspecified test); Control vs Pembrolizumab; p = 0.41648; Hazard Ratio (HR) 0.98 (95% CI 0.81 to 1.19); Regression, Cox; NCT02256436 ↗

registry analysis (unspecified test); Control vs Pembrolizumab; p = 0.00224; Hazard Ratio (HR) 0.73 (95% CI 0.59 to 0.91); Regression, Cox; NCT02256436 ↗

Publications

• Giannatempo P, Machiels JP, Sassa N, Arranz JA, Fujii Y, Su WP, Keam B, Culine S, Shen YC, Langa JM, Sarid D, Aarts M, Calabro F, Rosenbaum E, Moreno BH, Bavle A, Xu JZ, Rha SY. Impact of Histology on Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Advanced or Metastatic Urothelial Carcinoma in the Phase 3 KEYNOTE-045 and KEYNOTE-361 Trials. Clin Genitourin Cancer. 2025 Apr;23(2):102273. doi: 10.1016/j.clgc.2024.102273. Epub 2024 Nov 15.
• Balar AV, Castellano DE, Grivas P, Vaughn DJ, Powles T, Vuky J, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Necchi A, Petrylak DP, Plimack ER, Xu JZ, Imai K, Moreno BH, Bellmunt J, de Wit R, O'Donnell PH. Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up. Ann Oncol. 2023 Mar;34(3):289-299. doi: 10.1016/j.annonc.2022.11.012. Epub 2022 Dec 6.
• Bellmunt J, de Wit R, Fradet Y, Climent MA, Petrylak DP, Lee JL, Fong L, Necchi A, Sternberg CN, O'Donnell PH, Powles T, Plimack ER, Bajorin DF, Balar AV, Castellano D, Choueiri TK, Culine S, Gerritsen W, Gurney H, Quinn DI, Vuky J, Vogelzang NJ, Cristescu R, Lunceford J, Saadatpour A, Loboda A, Ma J, Rajasagi M, Godwin JL, Homet Moreno B, Grivas P. Putative Biomarkers of Clinical Benefit With Pembrolizumab in Advanced Urothelial Cancer: Results from the KEYNOTE-045 and KEYNOTE-052 Landmark Trials. Clin Cancer Res. 2022 May 13;28(10):2050-2060. doi: 10.1158/1078-0432.CCR-21-3089.
• Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.
• van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.
• Fradet Y, Bellmunt J, Vaughn DJ, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Nam K, Frenkl TL, Perini RF, de Wit R, Bajorin DF. Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up. Ann Oncol. 2019 Jun 1;30(6):970-976. doi: 10.1093/annonc/mdz127.
• Vaughn DJ, Bellmunt J, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Li H, Perini RF, Bajorin DF, de Wit R. Health-Related Quality-of-Life Analysis From KEYNOTE-045: A Phase III Study of Pembrolizumab Versus Chemotherapy for Previously Treated Advanced Urothelial Cancer. J Clin Oncol. 2018 Jun 1;36(16):1579-1587. doi: 10.1200/JCO.2017.76.9562. Epub 2018 Mar 28.
• Rassy EE, Bakouny Z, Aoun F, Haddad FG, Sleilaty G, Assi T, Kattan J. A network meta-analysis of the PD(L)-1 inhibitors in the salvage treatment of urothelial bladder cancer. Immunotherapy. 2018 Jun;10(8):657-663. doi: 10.2217/imt-2017-0190. Epub 2018 Mar 22.
• Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Poehlein CH, Perini RF, Bajorin DF; KEYNOTE-045 Investigators. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017 Mar 16;376(11):1015-1026. doi: 10.1056/NEJMoa1613683. Epub 2017 Feb 17.
• Kim YS, Lee SI, Park SH, Park S, Hwang IG, Lee SC, Sun JM, Lee J, Lim HY. A Phase II Study of Weekly Docetaxel as Second-Line Chemotherapy in Patients With Metastatic Urothelial Carcinoma. Clin Genitourin Cancer. 2016 Feb;14(1):76-81. doi: 10.1016/j.clgc.2015.09.008. Epub 2015 Sep 25.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Docetaxel	Small molecule	75 mg/m2	Intravenous
Comparator	Paclitaxel	Small molecule	175 mg/m2	Intravenous
Subject	Pembrolizumab	Monoclonal antibody	200 mg	Intravenous
Comparator	Vinflunine	Small molecule	320 mg/m2	Intravenous

Indications