ASCO GU 2018: Interim Results from PURE-01: A Phase 2, Open-Label Study of Neoadjuvant Pembrolizumab Before Radical Cystectomy for Muscle-Invasive Urothelial Bladder Carcinoma

San Francisco, CA ( invasive urothelial bladder cancer (MIUC) is an aggressive disease with more than 40% of patients developing recurrence after radical cystectomy (RC). Despite the fact that there is level 1 evidence demonstrating that cisplatin-based neoadjuvant chemotherapy confers an overall survival benefit1, it is administered in a minority of patients worldwide. Pembro is an EMA and FDA-approved standard therapy for metastatic urothelial carcinoma after platinum failure or for cisplatin-ineligible patients. The authors hypothesized that neoadjuvant pembro, could downstage MIUC and reduce recurrence.


PURE-01 (NCT02736266) is an open-label, single-arm, phase 2 study aiming to evaluate the activity, medical and surgical safety, and immune modulatory effects of pembro administered as a short window-of-opportunity course of therapy preceding RC. Eligibility criteria included: T2-T4aN0 stage, and residual disease after transurethral resection of the bladder (TURB, surgical opinion, cystoscopy or radiological presence). The study includes cisplatin eligible- and ineligible patients. Patients receive 3 cycles of pembro 200mg 3 weekly before RC (planned < 3 weeks of the last dose). Computed tomography (CT) scan, FDG-PET/CT scan, and bladder multipara metric magnetic resonance imaging (mpMRI) are done during screening and before RC. Radiologically non-responders to pembro (per investigator decision) are given 3 additional courses of dose-dense MVAC chemotherapy. After RC, patients are managed according to local guidelines (adjuvant chemotherapy vs observation). Further anti PD-1/PD-L1 therapy will not be given post-operatively. Pathologic complete response (pT0) is the primary endpoint. All patients enrolled who receive at least 1 cycle of study drug will be included in the intention to treat (ITT) analysis. The H1 hypothesis is pT0 ≥20% and H0 hypothesis is pT0≤10%. 

In a 2-stage design, 90 patients overall will be accrued (80% power and a 2-sided test of significance at the 10% level). Since Jan 30th 2018, 40/90 patients have been recruited so far. Activity results and early translational findings (immune-cell profiling) will be added, and may be regarded to as first data of preoperative immunotherapy before major surgery. Clinical trial information: NCT02736266

Presented by: Andrea Necchi, MD Milano, Italy

Co Authors: Alberto Briganti, Daniele Raggi, Patrizia Giannatempo, Luigi Mariani, Antonella Messina, Andrea Anichini, Giuseppina Calareso, Flavio Crippa, Mario Catanzaro, Nicola Fossati, Giorgio Gandaglia, Andrea Salonia, Roberto Salvioni, Francesco Montorsi; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Vita-Salute San Raffaele University, Urological Research Institute, IRCCS San Raffaele Hospital, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Urological Research Institute, IRCCS San Raffaele Hospital, Milano, Italy; Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA


1. Grossman  HB, Natale  RB, Tangen  CM, et al. Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer. New England Journal of Medicine 2003; 349(9): 859-66.