The PURE-01 (NCT02736266) 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, clinical stage T2-T4aN0M0 disease by CT, MRI or PET/CT within four weeks of randomization. Key exclusion criteria include patients previously treated with chemotherapy for bladder cancer, or malignancies within 5 years of bladder cancer diagnosis. Pembrolizumab is administered at the dose of 200mg, as a 30-minute INV infusion, every 3 weeks for a total of three cycles prior to radical cystectomy. The primary outcome is pathologic complete response at the time of radical cystectomy. Secondary outcomes include (i) adverse events, (ii) percentage of treatment-related delay in surgery, and (iii) Frequency of treatment-related adverse events.
Currently, 60 patients have been enrolled in this study and 37 patients have evaluable data thus far. The median age of these patients was 66 years (IQR 60-73), most were males (84%), and five had had prior DD-MVAC prior to pembrolizumab. The most common cystectomy modality was the robotic approach (68%), and 49% of patients had a neobladder. Adjuvant chemotherapy was administered in two patients. The most common any-cause adverse event was thyroid dysfunction (16.2%), with only two (5.4%) grade 3/4 adverse events from pembrolizumab. Impressively, the pathologic complete response rate was 40.5% (n=15), and pathologic downstaging was seen in 51.3% (n=19) patients. There were 9 patients with ypTany ypN+ disease, and 4 patients with ypT2-4 ypN0 at the time of radical cystectomy (considered treatment failures). The mean tumor burden for pT0 patients was 13.16 Mut/Mb and for non-pT0 patients was 9.78 Mut/Mb. This trial is currently recruiting, with a targeted 90 patients to be enrolled and completed by early-mid 2019.
Dr. Necchi concluded with several take-home points from this exciting phase II neoadjuvant immunotherapy trial:
- Pembrolizumab is safe in the neoadjuvant setting
- Results of the tumor burden assessment in association with pathologic response likely reflects different biologic features and key differences between early and advanced stage
- Full clinical and biomarker results of PURE-01 will be presented at ASCO 2018
- 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.
- 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, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Co-Authors: Alberto Briganti, Milano, Italy, Daniele Raggi, Patrizia Giannatempo, Milan, Italy, Marco Bianchi, Milano, Italy, Luigi Mariani, Antonella Messina, Andrea Anichini, Milan, Italy, Massimo Freschi, Milano, Italy, Maurizio Colecchia, Roberto Salvioni, Milan, Italy, Renzo Colombo, Andrea Gallina, Francesco Montorsi, Milano, Italy
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, @zklaassen_md at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA