Patients and methods: PURE-02 was a feasibility study enrolling individuals with UTUC, at clinical stage N0M0, with high-risk features according to the modified European Association of Urology definition, based on the presence of either: high-grade disease, multifocality, tumor size ≥2 cm, and/or hydronephrosis. The treatment consisted of 3 courses of 200 mg pembrolizumab, intravenously, every 3 weeks, followed by radical nephroureterectomy (RNU). The endpoints were to assess the safety, pathological responses, and biomarkers.
Results: Ten patients were enrolled between August 2018 and November 2020, 9 (90%) completed the neoadjuvant course. One treatment-related death occurred as a complication of severe myocarditis, myasthenia gravis, hepatitis and myositis. One (14.3%) patient achieved a clinical complete response and refused to undergo RNU. Two (20%) had disease progression and received subsequent chemotherapy, prior to RNU. Overall, 7 patients underwent RNU: one (14.3%) achieved an ypT1N0 response, although this patient was reported to have a cT1 tumor at baseline imaging. The remaining patients were nonresponders. Circulating tumor DNA assay did not identify patients likely to achieve a complete pathologic response.
Conclusion: Single-agent neoadjuvant pembrolizumab did not appear to be a promising treatment strategy for patients with biomarker-unselected, high-risk localized UTUC.
Andrea Necchi1, Alberto Martini 2, Daniele Raggi 3, Vito Cucchiara 2, Maurizio Colecchia 4, Roberta Lucianò 5, Luca Villa 2, Elio Mazzone 2, Giuseppe Basile 2, Simone Scuderi 2, Filippo Pederzoli 2, Marco Bandini 2, Francesco Barletta 2, Alessandro Larcher 2, Umberto Capitanio 2, Andrea Salonia 6, Alberto Briganti 6, Jeffrey S Ross 7, Antonella Messina 8, Francesco Montorsi 6
- Vita-Salute San Raffaele University; Department of Medical Oncology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy. Electronic address: .
- Department of Urology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy.
- Department of Medical Oncology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy.
- Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
- Department of Pathology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy.
- Vita-Salute San Raffaele University; Department of Urology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy.
- Foundation Medicine Inc., Cambridge, MA; Upstate Medical University, New York, NY.
- Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Source: Necchi A, Martini A, Raggi D, et al. "A feasibility study of preoperative pembrolizumab before radical nephroureterectomy in patients with high-risk, upper tract urothelial carcinoma: PURE-02." Urol Oncol. 2021. S1078-1439(21)00220-9.