Sasanlimab plus BCG in BCG-naive, high-risk non-muscle invasive bladder cancer : the randomized phase 3 CREST trial
Shore, Neal (START Carolinas/Carolina Urologic Research Center (Myrtle Beach, Estats Units d'Amèrica))
Powles, Thomas (Queen Mary University of London)
Bedke, Jens (Klinikum Stuttgart)
Galsky, Matthew (Mount Sinai (Nova York, Estats Units d'Amèrica))
Palou, Juan (Universitat Autònoma de Barcelona)
Ku, Ja Hyeon (Seoul National University Hospital)
Kretkowski, Michal (Spolka z Ograniczona (Polònia))
Xylinas, Evanguelos (Université de Paris Cité)
Alekseev, Boris (P. Hertsen Moscow Cancer Research Institute (Moscú, Rússia))
Ye, Dingwei (Fudan University Shanghai Cancer Center)
Guerrero-Ramos, Félix (Hospital Universitario 12 de Octubre (Madrid))
Briganti, Alberto (IRCCS San Raffaele Scientific Institute (Milà, Itàlia))
Kulkarni, Girish S. (Center University of Toronto)
Brinkmann, Julia (Pfizer Pharma GmbH (Berlin, Alemanya))
Calella, Anna-Maria (Pfizer (Roma, Itàlia))
Cesari, Rossano (Pfizer (Roma, Itàlia))
Eccleston, Anthony (Pfizer (Tadworth, Regne Unit))
Michelon, Elisabete (Pfizer (New York, Estats Units))
Vermette, Jennifer (Pfizer (Cambridge, Estats Units d'Amèrica))
Wei, Caimiao (Pfizer (Groton, Estats Units d'Amèrica))
Steinberg, Gary D. (Rush University Medical Center (Chicago, Estats Units d'Amèrica))

Data:	2025
Resum:	Bacillus Calmette-Guérin (BCG) induction and maintenance (I+M) after transurethral resection of bladder tumor is standard of care (SOC) in high-risk non-muscle invasive bladder cancer (NMIBC). However, disease recurrence/progression occurs in approximately 40% of patients at 2 years, with unfavorable prognosis. Limited bladder-sparing therapeutic options exist, and no improvements to response durability have been observed in decades. CREST is a global, phase 3, randomized trial evaluating subcutaneous sasanlimab in combination with BCG-I+M (Arm A), sasanlimab in combination with BCG-I (Arm B) or BCG-I+M (Arm C) in BCG-naive high-risk NMIBC. The primary endpoint was investigator-assessed event-free survival (EFS) for Arm A versus Arm C; key secondary endpoints were EFS (Arm B versus Arm C) and overall survival. Patients were randomized 1:1:1 to Arm A (N = 352), Arm B (N = 352) and Arm C (N = 351). The trial met its primary endpoint with a statistically significant and clinically meaningful prolongation of EFS (Arm A versus Arm C); hazard ratio, 0. 68 (95% confidence interval: 0. 49-0. 94); one-sided P = 0. 0095. The 36-month estimated EFS rates were 82. 1% (Arm A) and 74. 8% (Arm C). EFS benefit for Arm A versus Arm C was observed across prespecified subgroups, including carcinoma in situ (CIS) and T1. The safety profile of the combination was consistent with the known profiles. To our knowledge, sasanlimab is the first anti-PD-1 antibody to show a clinically meaningful prolongation of EFS when combined with BCG-I+M versus SOC in patients with BCG-naive high-risk NMIBC. Sasanlimab combined with BCG-I+M has the potential to redefine the treatment paradigm and clinical decision-making for patients with BCG-naive high-risk NMIBC. ClinicalTrials. gov identifier: . As presented at the 2025 ASCO Annual Meeting: in a randomized controlled phase 3 trial evaluating subcutaneous administration of sasanlimab, an anti-PD-1 inhibitor, with Bacillus Calmette-Guérin induction and maintenance treatment, combination treatment significantly improved event-free survival versus standard-of-care therapy.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Bladder cancer
Publicat a:	Nature Medicine, Vol. 31 (may 2025) , p. 2806-2814, ISSN 1546-170X

DOI: 10.1038/s41591-025-03738-z
PMID: 40450141

25 p, 3.4 MB

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