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Performance of pre- and post-pembrolizumab vesical imaging–reporting and data system (VI-RADS) to predict the pathological response and efficacy outcomes in muscle-invasive urothelial bladder cancer (MIBC): Full data analysis from the PURE-01 trial.

2023; Lippincott Williams & Wilkins; Volume: 9; Issue: Supplement_1 Linguagem: Inglês

10.1200/go.2023.9.supplement_1.65

2687-8941

Chiara Mercinelli, Giorgio Brembilla, Giuseppe Basile, Ewan A. Gibb, Daniele Raggi, Giuseppina Calareso, Tiago Costa de Pádua, Laura Marandino, Damiano Alfio Patanè, Emanuele Crupi, Andrea Del Prete, Patrizia Giannatempo, Marco Moschini, Jeffrey S. Ross, Alberto Briganti, Francesco Montorsi, A. Messina, Francesco De Cobelli, Andrea Necchi,

Cancer Immunotherapy and Biomarkers

65 Background: The VI-RADS is a standardized reporting system that uses multiparametric magnetic resonance imaging (mpMRI) parameters to differentiate non muscle-invasive bladder cancer (NMIBC) from MIBC. Limited data on clinical response assessment to neoadjuvant therapy are currently available. In this study, we aimed to analyze the performance of VI-RADS to predict the pT0 or pT≤1 response post-neoadjuvant immunotherapy in MIBC. Methods: In PURE-01 study (NCT02736266) patients (pts) were staged with mpMRI before and after treatment (3 cycles of Pembrolizumab) prior to radical cystectomy (RC). Logistic regression models analyzed pre- and post-pembro VI-RADS, with clinical and tumor-related variables, against ypT≤1N0 (primary endpoint) and ypT0N0 (secondary endpoint). VI-RADS scores were dichotomized between 0-3 (0 = no evidence of disease) and 4-5 (5 = extension to extravescical fat). Event-free survival (EFS) and overall survival (OS) analyses based on VI-RADS were performed. Comprehensive genomic profiling and transcriptome-wide expression profiling data were matched with VI-RADS scores. Model performance was also tested in the ongoing NureCombo (nivolumab+nab-paclitaxel; NCT04876313) and SURE-01 (sacituzumab govitecan; NCT05226117) neoadjuvant studies. Results: In total, 110 patients treated with neoadjuvant pembrolizumab between 02/2017 and 07/2020 had centrally reviewed scans (N=220 mpMRI). Pre-pembrolizumab, 21 patients (19.1%) had no measurable disease (VI-RADS=0), 34 (30.9%) had a VI-RADS 1-3 score, and 55 (50%) had a VI-RADS 4-5 score. Both pre-pembrolizumab and post-pembrolizumab VI-RADS 0-3 scores were the only significant covariates that predicted the ypT≤1N0 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembrolizumab VI-RADS 0-3 predicting the ypT≤1N0 response (odds ratio [OR]: 23.4, 95%CI: 7-95.3, p<0.0001). The area-under-the-curve (AUC) of this model was 0.90. Post-pembrolizumab VI-RADS 0-3 also predicted longer EFS (p<0.001) and OS (p=0.044). The scores of several gene signatures from baseline tumors differed between pre-pembrolizumab VI-RADS 0-3 and 4-5 categories. RAF1 mutations were enriched in pre-pembrolizumab VI-RADS 0-3 group (p=0.045). Conclusions: VI-RADS scores post-pembrolizumab revealed a robust association with pathological downstaging and survival. VI-RADS scores were also characterized by distinct biomarker features. These results indicate that VI-RADS is emerging as an important tool to design next-generation trials in MIBC. Clinical trial information: NCT02736266 .