The PURE-01 study (NCT02736266) pioneered the neoadjuvant immune-checkpoint inhibitor (ICI) therapy before radical cystectomy (RC) in patients with muscle-invasive urothelial bladder carcinoma (MIBC). We herein present the survival outcomes after a median follow-up of three years.
The intention-to-treat (ITT) population included 155 patients. Event-free survival (EFS) was defined as the time from pembrolizumab initiation until radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy, recurrence after RC, or death. Further outcomes were recurrence-free survival (RFS) post-RC and overall survival (OS). Multivariable Cox regression analyses for EFS were performed. Kaplan-Meir analyses compared EFS outcomes according to baseline programmed cell-death-ligand-1 (PD-L1) combined positive score (CPS) and according to the molecular subtypes.
After a median [interquartile range (IQR)] follow-up of 39 (30-47) months, 36-month EFS and OS were 74.4% [95% confidence interval (CI): 67.8-81.7] and 83.8% (95% CI: 77.8- 90.2) in ITT population, respectively. Overall, 143 (92.3%) patients underwent RC. Within the cohort of patients who did not receive additional chemotherapy (N=125), 36-months RFS was 96.3% (95%CI) (91.6-100) for patients achieving a ypT0N0, 96.1% (89-100) for ypT1/a/isN0, 74.9% (60.2-93) for ypT2-4N0, and 58.3% (36.2-94.1) for ypT any N1-3 response. EFS was significantly stratified among PD-L1 tertiles (lower tertile: 59.7% vs medium tertile: 76.7% vs higher tertile: 89.8%, p=0.0013). The claudin-low and basal/squamous subtypes displayed the lowest rates of events.
At a median follow-up of three-years, PURE-01 results further confirm the sustained efficacy of neoadjuvant pembrolizumab before RC. PD-L1 expression was the strongest predictor of sustained response post-RC.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 Oct 03 [Epub ahead of print]
Giuseppe Basile, Marco Bandini, Ewan A Gibb, Jeffrey S Ross, Daniele Raggi, Laura Marandino, Tiago Costa de Padua, Emanuele Crupi, Renzo Colombo, Maurizio Colecchia, Roberta Lucianò, Luigi Nocera, Marco Moschini, Alberto Briganti, Francesco Montorsi, Andrea Necchi
IRCCS San Raffaele Hospital, Milan, Italy., Veracyte, Inc., Vancouver, British Columbia, Canada., Upstate Medical University, Syracuse, NY, United States., Ospedale San Raffaele, Milan, Italy., University Vita-Salute San Raffaele, Milan, Italy., IRCCS San Raffaele Hospital; Vita-Salute San Raffaele University, Milan, Italy., IRCCS OSR, Italy., Department of Urology, Vita Salute San Raffaele University, Milan, Italy, Italy.