The PURE-01 trial is an open-label, single-arm, phase 2 study in Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy to evaluate the activity, medical and surgical safety, and immune modulatory effects of pembrolizumab administered prior to radical cystectomy. Key inclusion criteria for this trial included patients with:
- Predominantly urothelial carcinoma histology (>50%)
- Clinical stage ≤3bN0M0 disease by CT, MRI or PET/CT within four weeks of randomization.
- Residual disease after TURBT
- GFR ≥20 ml/min
- ECOG performance status 0-1
The study started enrolling patients in February 2017, and at a data cutoff of May 10, 2018 the median follow-up for PURE-01 was 8 months. The first stage of enrollment included 43 patients, the results of which are discussed herein. Among these patients were 35 males/7 females, with 37.2% of patients with cT2N0 disease, 58.1% with cT3N0, and 4.7% of patients with T2-3N1. At the time of this analysis, there were 17/43 patients that were pT0 (39.5%, 95%CI: 26.3-54.4) and 5 <pT2 (total <pT2 rate: 51.2%). Treatment failures were categorized as follows:
- ypT2-4 ypN0: n=7, 16.3%
- ypTany ypN+: n=9, 20.9%
- Clinical failure (additional neoadjuvant chemotherapy): n=5, 11.6%
Necchi concluded with several important messages:
- Neoadjuvant pembrolizumab was associated with few side effects, did not delay surgery, and induced a complete pathological response in nearly 40% of patients
- Immune genomic features and their modulation were disclosed in the non-metastatic setting
- DDR, RB1 genomic alterations and PD-L1 CPS may constitute the algorithm for selecting which patients deserve a bladder-sparing approach after response assessment: ie. TURBT pembrolizumab re-TURB maintenance pembrolizumab.
1. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349(9):859-866.
2. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017;376(11):1015-1026.
Presented by: Andrea Necchi, MD, Istituto Nazionale dei Tumori, Milan, Italy
Co-Authors: Alberto Briganti, Marco Bianchi, Daniele Raggi, Patrizia Giannatempo, Roberta Luciano', Maurizio Colecchia, Simona Massa, Marco Bandini, Nicola Fossati, Giorgio Gandaglia, Renzo Colombo, Andrea Gallina, Andrea Salonia, Roberto Salvioni, Siraj Mahamed Ali, Jeffrey S. Ross, Jon Chung, Francesco Montorsi; Vita-Salute San Raffaele University, Urological Research Institute, IRCCS San Raffaele Hospital, Milan, Italy; Vita Salute San Raffaele University and Urological Research Institute (URI), IRCCS San Raffaele Hospital, Milano, Italy; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; IRCCS San Raffaele Hospital, Milano, Italy; Vita-Salute San Raffaele University, Milan, Italy; IRCCS Ospedale San Raffaele, Milan, Italy; Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Urological Research Institute, IRCCS San Raffaele Hospital, Milano, Italy; Foundation Medicine, Inc., Cambridge, MA; SUNY Upstate Medical University, Syracuse, NY; Universita Vita Salute San Raffaele, Milan, Italy
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA