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
- PMID: 40037029
- DOI: 10.1016/j.clgc.2024.102273
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
Abstract
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).
Keywords: Immunotherapy; PD-1 inhibitor; Platinum-refractory; Post hoc; Transitional cell carcinoma.
Copyright © 2024. Published by Elsevier Inc.
Conflict of interest statement
Disclosure Patrizia Giannatempo has received personal fees for consulting from Astellas, Janssen, Merck & Co., Inc., MSD, and Pfizer; has received honoraria from Astellas, Janssen, Merck & Co., Inc., and MSD; has received payment for expert testimony from Astellas; and has received travel support for meeting attendance from Merck & Co., Inc. and Pfizer. Jean-Pascal Machiels has received institutional support for advisory board participation from ALX Oncology, Astellas, Bayer, Boerhinger, Bristol Myers Squibb, Cue Biopharma, CureVac, eTheRNA, F-Star, Genmab, GSK, Incyte, iTEOS, IPSEN, Merck Serono, Merus, MSD, NEKTAR, Novartis, Pfizer, Roche, and Seagen; and has received travel support for meeting attendance from Amgen, Bristol Myers Squibb, Gilead, Merck Serono, MSD, Pfizer, and Sanofi. Naoto Sassa, Wen-Pin Su, Ying-Chun Shen, and Eli Rosenbaum have nothing to disclose. Jose Angel Arranz has received personal fees for advisory board participation from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Merck & Co., Inc., MSD, Novartis, and Pfizer; has received honoraria from Astellas, Bristol Myers Squibb, and Ipsen; and has received travel support from Bristol Myers Squibb and Merck & Co., Inc. Yasuhisa Fujii has received honoraria from Merck & Co., Inc., MSD, and Ono. Bhumsuk Keam has received grants from AstraZeneca, MSD Oncology, and Ono Pharmaceutical; and has received personal fees for consulting from Celid, Handok, ImmuneOncia, MSD Oncology, NeoImmuneTec, and Trialinformatics; and has received honoraria from Merck & Co., Inc. and MSD Oncology. Stéphane Culine received personal fees for consulting from Astellas, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Merck & Co., Inc., MSD, and Takéda and travel support from Astellas, Astra-Zeneca, Chugaï, and Janssen. José Muñoz Langa has received nonfinancial support for meeting attendance from AstraZeneca, GSK, and MSD. David Sarid has received consulting fees and honoraria for lectures or presentations from MSD. Maureen Aarts has received personal fees for advisory board participation from Amgen, Astellas, Bayer, Bristol Myers Squibb, Merck-Pfizer, MSD, Novartis, Pierre Fabre, and Sanofi; has received honoraria and travel support from Ismar Health NV; and has received institutional research grants from Merck-Pfizer. Fabio Calabrò has received travel support from Novartis; and has participated in data safety monitoring boards or advisor boards for Astellas, AstraZeneca, Ipsen, Johnson & Johnson, MSD, Novartis, and Pfizer. Blanca Homet Moreno, Abhishek Bavle, and Jin Z. Xu are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and own stock in Merck & Co., Inc., Rahway, NJ, USA. Sun Young Rha has received institutional research grants from ABLBIO, ALX Oncology, Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, BeiGene, Bold Therapeutics, Daiichi Sankyo, Eisai, Ipsen, Leap Therapeutics, Macrogenics, MedPacto, Merck KGaA, Merck Sharpe and Dohme, MSD, Ono Pharmaceutical, Pfizer, Seagen, Taiho Pharmaceutical, and Zymeworks; has received consulting fees from Indivumed and LG Biochem; has received honoraria from Amgen, Astellas, Daiichi Sankyo, Eisai, Ipsen, Lilly, MSD, and Sanofi; and has participated in data safety monitoring boards or advisory boards for Amgen, Arcus, and Toray.
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