TY - JOUR
T1 - 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
AU - Giannatempo, Patrizia
AU - Machiels, Jean Pascal
AU - Sassa, Naoto
AU - Arranz, Jose Angel
AU - Fujii, Yasuhisa
AU - Su, Wen Pin
AU - Keam, Bhumsuk
AU - Culine, Stéphane
AU - Shen, Ying Chun
AU - Langa, José Muñoz
AU - Sarid, David
AU - Aarts, Maureen
AU - Calabrò, Fabio
AU - Rosenbaum, Eli
AU - Moreno, Blanca Homet
AU - Bavle, Abhishek
AU - Xu, Jin Z.
AU - Rha, Sun Young
N1 - Funding Information:
The authors thank the patients and their families and caregivers, all primary investigators, and site personnel for participating in the KEYNOTE studies. Medical writing and/or editorial assistance was provided by Bresler Swanepoel, PhD, Shane Walton, PhD, and Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. Inc. Rahway, NJ, USA. The research and preparation of the manuscript were supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. Inc. Rahway, NJ, USA. The study funder had a role in the study design, data collection, data analysis, data interpretation, and writing of the report. The funder maintained the study database and ensured that data were collected according to the protocol. All authors reviewed the final version of the manuscript to be submitted and agree with its content and submission.
Publisher Copyright:
© 2024
PY - 2025/4/1
Y1 - 2025/4/1
N2 - Introduction: A post hoc analysis of efficacy and safety outcomes with pembrolizumab monotherapy was conducted in patients with advanced or metastatic urothelial carcinoma (UC) with pure transitional cell carcinoma (TCC) or mixed predominant TCC histology enrolled in the phase 3 KEYNOTE-045 and KEYNOTE-361 studies. Methods: Adults with platinum-refractory advanced or metastatic UC who received pembrolizumab monotherapy in KEYNOTE-045 and adults with advanced or metastatic UC and no prior systemic chemotherapy who received pembrolizumab monotherapy in KEYNOTE-361 were analyzed separately. Pembrolizumab 200 mg was administered intravenously every 3 weeks for =2 years. Histology was assessed by investigator. End points included objective response rate (ORR), progression-free survival, and duration of response per RECIST v1.1 by central radiology assessment, as well as overall survival (OS) and safety. Results: In KEYNOTE-045, 268 patients had known histology (pure TCC: 186; mixed predominant TCC: 82). At data cutoff (October 1, 2020), median follow up was 62.9 months (range, 59.0-70.9). For pure TCC, confirmed ORR was 21.0% (95% CI, 15.4-27.5); median OS was 9.7 months (95% CI, 7.5-11.8). For mixed predominant TCC, confirmed ORR was 24.4% (95% CI, 15.6-35.1); median OS was 11.6 months (95% CI, 7.4-16.4). In KEYNOTE-361, 307 patients had known histology (pure TCC: 280; mixed predominant TCC: 27). At data cutoff (April 29, 2020), median follow-up was 32.5 months (range, 22.0-42.3). For pure TCC, confirmed ORR was 29.3% (95% CI, 24.0-35.0); median OS was 14.8 months (95% CI, 11.8-17.9). For mixed predominant TCC, confirmed ORR was 40.7% (95% CI, 22.4-61.2); median OS was 16.2 months (95% CI, 5.5-NR). Grade 3-5 treatment-related adverse events occurred at similar rates for treated patients in both studies. Conclusion: In this post hoc analysis, efficacy and safety outcomes with pembrolizumab monotherapy were generally consistent for patients with advanced or metastatic UC in KEYNOTE-045 and KEYNOTE-361 studies between histology subgroups. Clinical Trial Registration: ClinicalTrials.gov, KEYNOTE-045 (NCT02256436) and KEYNOTE-361 (NCT02853305)
AB - Introduction: A post hoc analysis of efficacy and safety outcomes with pembrolizumab monotherapy was conducted in patients with advanced or metastatic urothelial carcinoma (UC) with pure transitional cell carcinoma (TCC) or mixed predominant TCC histology enrolled in the phase 3 KEYNOTE-045 and KEYNOTE-361 studies. Methods: Adults with platinum-refractory advanced or metastatic UC who received pembrolizumab monotherapy in KEYNOTE-045 and adults with advanced or metastatic UC and no prior systemic chemotherapy who received pembrolizumab monotherapy in KEYNOTE-361 were analyzed separately. Pembrolizumab 200 mg was administered intravenously every 3 weeks for =2 years. Histology was assessed by investigator. End points included objective response rate (ORR), progression-free survival, and duration of response per RECIST v1.1 by central radiology assessment, as well as overall survival (OS) and safety. Results: In KEYNOTE-045, 268 patients had known histology (pure TCC: 186; mixed predominant TCC: 82). At data cutoff (October 1, 2020), median follow up was 62.9 months (range, 59.0-70.9). For pure TCC, confirmed ORR was 21.0% (95% CI, 15.4-27.5); median OS was 9.7 months (95% CI, 7.5-11.8). For mixed predominant TCC, confirmed ORR was 24.4% (95% CI, 15.6-35.1); median OS was 11.6 months (95% CI, 7.4-16.4). In KEYNOTE-361, 307 patients had known histology (pure TCC: 280; mixed predominant TCC: 27). At data cutoff (April 29, 2020), median follow-up was 32.5 months (range, 22.0-42.3). For pure TCC, confirmed ORR was 29.3% (95% CI, 24.0-35.0); median OS was 14.8 months (95% CI, 11.8-17.9). For mixed predominant TCC, confirmed ORR was 40.7% (95% CI, 22.4-61.2); median OS was 16.2 months (95% CI, 5.5-NR). Grade 3-5 treatment-related adverse events occurred at similar rates for treated patients in both studies. Conclusion: In this post hoc analysis, efficacy and safety outcomes with pembrolizumab monotherapy were generally consistent for patients with advanced or metastatic UC in KEYNOTE-045 and KEYNOTE-361 studies between histology subgroups. Clinical Trial Registration: ClinicalTrials.gov, KEYNOTE-045 (NCT02256436) and KEYNOTE-361 (NCT02853305)
KW - Immunotherapy
KW - PD-1 inhibitor
KW - Platinum-refractory
KW - Post hoc
KW - Transitional cell carcinoma
U2 - 10.1016/j.clgc.2024.102273
DO - 10.1016/j.clgc.2024.102273
M3 - Article
SN - 1558-7673
VL - 23
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 2
M1 - 102273
ER -