Cisplatin- or Carboplatin-Based Chemotherapy Plus Pembrolizumab in Advanced Urothelial Cancer: Exploratory Analysis From the Phase 3 KEYNOTE-361 Study.

Autor: Powles T; Barts Cancer Centre, Barts Health NHS Trust Biomedical Research Center, Queen Mary University of London, London, United Kingdom. Electronic address: thomas.powles1@nhs.net., Csőszi T; County Oncology Centre, Hetényi Géza Hospital, Szolnok, Hungary., Loriot Y; Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France., Matsubara N; National Cancer Center Hospital East, Kashiwa, Japan., Geczi L; Medical Oncology Center, National Institute of Oncology, Budapest, Hungary., Cheng SY; Sunnybrook Health Sciences Centre‒Odette Cancer Centre, Toronto, ON, Canada., Fradet Y; CHU de Québec-Université Laval, Quebec City, QC, Canada., Alva A; Department of Internal Medicine-Hematology/Oncology, University of Michigan Health System, Ann Arbor, MI., Oudard S; Georges Pompidou European Hospital, University Paris Cité, Paris, France., Vulsteke C; Department of Medical Oncology, Maria Middelares Hospital, Gent, Belgium; Center for Oncological Research (CORE), University of Antwerp, Antwerp, Belgium., Morales-Barrera R; Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain., Fléchon A; Centre Léon Bérard, Lyon, France., Gunduz S; Department of Medical Oncology, Koc University Hospital, Istanbul, Türkiye., Liu CC; Merck & Co., Inc., Rahway, NJ., Moreno BH; Merck & Co., Inc., Rahway, NJ., Bavle A; Merck & Co., Inc., Rahway, NJ., Özgüroğlu M; Division of Medical Oncology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Türkiye.
Jazyk: angličtina
Zdroj: Clinical genitourinary cancer [Clin Genitourin Cancer] 2025 Feb; Vol. 23 (1), pp. 102261. Date of Electronic Publication: 2024 Nov 01.
DOI: 10.1016/j.clgc.2024.102261
Abstrakt: Introduction: KEYNOTE-361 evaluated first-line pembrolizumab with and without platinum-based chemotherapy versus chemotherapy alone in advanced or metastatic urothelial carcinoma. The primary end points of progression-free survival (PFS) or overall survival (OS) were not met. Exploratory analysis of efficacy by platinum agent (cisplatin or carboplatin) is reported.
Patients and Methods: Eligible patients were randomly assigned 1:1:1 to receive pembrolizumab 200 mg intravenously every 3 weeks for ≤35 cycles with or without chemotherapy (gemcitabine with investigator's choice of either cisplatin or carboplatin) or chemotherapy alone. This exploratory subset analysis evaluated PFS and objective response rate (ORR) per RECIST v1.1 by blinded independent central review and OS for cisplatin- or carboplatin-based chemotherapy with versus without pembrolizumab for patients assigned to chemotherapy-containing arms of KEYNOTE-361.
Results: Of 1010 patients enrolled, 703 were assigned to receive a chemotherapy-containing regimen (n = 312 cisplatin based; n = 391 carboplatin based). Median follow-up was 31.3 months. For cisplatin-based arms, with versus without pembrolizumab, median OS was 20.1 versus 16.4 months (HR 0.88, 95% CI, 0.67-1.15) and median PFS was 8.5 versus 7.1 months (HR 0.67, 0.51-0.89). ORR was 64.1% versus 48.7%, respectively. For carboplatin-based arms, with versus without pembrolizumab, median OS was 15.5 versus 12.3 months (HR 0.84, 95% CI, 0.67-1.06) and median PFS was 8.0 versus 6.7 months (HR 0.86, 0.68-1.09). ORR was 47.2% versus 41.8%, respectively. Among patients in the cisplatin-based versus carboplatin-based chemotherapy alone arms, 55.8% versus 41.8% received a subsequent antiprogrammed cell death protein 1/ligand 1 therapy. The addition of pembrolizumab did not significantly increase the incidence of adverse events reported.
Conclusion: Results suggest trends toward OS and PFS improvements with the addition of pembrolizumab to gemcitabine-platinum doublet over gemcitabine-platinum alone regardless of whether cisplatin or carboplatin was the chosen platinum agent. OS may have been influenced by active subsequent therapies.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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