Presentation Authors: Andrea Necchi*, Marco Bandini, Andrea Gallina, Marco Bianchi, Daniele Raggi, Antonella Messina, Milan, Italy, Jon Chung, Siraj Ali, Jeffrey Ross, Cambridge, MA, Andrea Anichini, Andrea Anichini, Maurizio Colecchia, Giorgio Gandaglia, Nicola Fossati, Simone Scuderi, Filippo Pederzoli, Andrea Salonia, Renzo Colombo, Alberto Briganti, Francesco Montorsi, Milan, Italy
Introduction: PURE-01 is a phase 2 study of Pembro before RC in MIBC: the primary endpoint (pathologic complete response [pT0]) was met in advance (Necchi et al. JCO 2018).While the study is still recruiting patients (pts), we analyzed the interim long-term outcomes in terms of relapse-free survival (RFS) and the role of multiparametric bladder magnetic resonance imaging (mpMRI) in predicting major pathologic response (pT < 2) in RC.
Methods: Pts with clinical stage T2-3bN0M0 received 3 courses of 200mg Pembro, before RC. Pts were staged and re-assessed with mpMRI before RC. 1-y RFS (overall and by pathologic stage) after Pembro and RC was compared with that from clinical stage-matched cohort of San Raffaele Urological Institute (URI, n=1021) and of the RISC multicenter database (n=719, Bandini et al, Eur Urol Oncol 2018).mpMRI were performed in all pts through bladder catheterization. The apparent diffusion coefficient (ADC) changes post-Pembro were matched with pathologic response, qPCR and genomic data from RC samples (FoundationONE).
Results: 70 pts have completed treatment thus far: with 27 pT0 (38.6%) and 44 pT < 2 (62.9%), activity was confirmed. 21 pts had â‰¥1y follow-up and were analyzed. Overall, 1-y RFS (95%CI) in PURE-01, URI and RISC were: 95.2 (86.6-100), 79.0 (76-82), and 69.7 (66.2-73.4). 1-y RFS after neoadjuvant chemotherapy and RC in URI and RISC were: 76.7 (61-97), and 76.5 (71-83).1-y RFS for pT3-4 and/or pN+ pts were: 88.9 (71-100), 71.2 (67-76), and 57.1 (52-62).39 pts had measurable disease for pre-post mpMRI changes. Pts with pT < 2 (n=16) on RC showed a median â€œmean ADCâ€ of 0.98 mm2/s vs 0.84 mm2/s of non-responders (NR, n=23, p=0.098), despite an increased T-cell infiltrate. Pts with cell-cycle gene alterations in RC (n=8) were all NR and showed lower median â€œmean ADCâ€ values (p=0.074).
Conclusions: The early efficacy data further support the role of single-agent IO as neoadjuvant therapy in MIBC. Pembro may be beneficial at long-term also in pathologically high-risk pts, thus questioning the value of PD-L1 for pt selection, as well as the role of pathologic response as surrogate of survival outcome post-checkpoint inhibition. mpMRI and genomic data might help identifying those pts who may need re-TURB only instead of RC.
Source of Funding: Merck & Co.