Initial studies of preoperative checkpoint inhibition before radical cystectomy (RC) have shown promising pathologic complete responses. We aimed to analyze the survival outcomes of patients enrolled in PURE-01 study (NCT02736266).
We report the results of the secondary endpoints of PURE-01 in the final population of 143 patients. In particular, we report the event-free survival (EFS) outcomes, defined as the time from the first cycle of pembrolizumab to radiographic disease progression precluding radical cystectomy (RC), initiation of neoadjuvant chemotherapy (NAC), recurrence after RC, or death from any cause. Other endpoints were recurrence-free survival (RFS) and overall survival (OS). Subgroup analyses were performed, including pathological response category, clinical complete responses (CR) assessed via multiparametric magnetic resonance imaging (mpMRI), and molecular subtyping. Cox regression analyses for EFS were also performed.
After a median (interquartile range [IQR]) follow-up of 23 (15-29) months, 12- and 24-month EFS was 84.5% (95% confidence interval [CI]: 78.5-90.9) and 71.7% (62.7-82). The prognosis was favorable across all the different pathological response subgroups, with the exception of ypN+ (N=21), showing a 24-month RFS (95% CI) of 39.3% (19.2-80.5). A statistically significant EFS benefit was observed in patients with a clinical CR (p=0.002). Programmed cell-death-ligand-1 combined positive score was significantly associated with longer EFS in multivariable analyses. Four patients refused RC after clinical evidence of CR, and none of them have recurred after a median follow-up of 10 months (IQR: 11-15). The claudin-low subtype displayed a numerically longer EFS after pembrolizumab and RC compared to the other subtypes.
The EFS results from PURE-01 revealed that the immunotherapy effect was maintained post-RC in most patients. Pembrolizumab compared favorably with neoadjuvant chemotherapy, irrespective of the biomarker status. Molecular subtyping may be a useful tool to select the patients who are predicted to benefit the most from neoadjuvant pembrolizumab.
Annals of oncology : official journal of the European Society for Medical Oncology. 2020 Sep 23 [Epub ahead of print]
M Bandini, E A Gibb, A Gallina, D Raggi, L Marandino, M Bianchi, J S Ross, M Colecchia, G Gandaglia, N Fossati, F Pederzoli, R Lucianò, R Colombo, A Salonia, A Briganti, F Montorsi, A Necchi
Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy., Decipher Biosciences Inc., Vancouver, Canada., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Foundation Medicine Inc., Cambridge, MA, United States; Upstate Medical University, Syracuse, NY, United States., Department of Pathology, IRCCS Ospedale San Raffaele, Milan, Italy., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;. Electronic address: .