Andrea Necchi1, Alberto Martini2, Daniele Raggi3, Vito Cucchiara2, Maurizio Colecchia4, Roberta Lucianò5, Luca Villa2, Elio Mazzone2, Giuseppe Basile2, Simone Scuderi2, Filippo Pederzoli2, Marco Bandini2, Francesco Barletta2, Alessandro Larcher2, Umberto Capitanio2, Andrea Salonia6, Alberto Briganti6, Jeffrey S Ross7, Antonella Messina8, Francesco Montorsi6. 1. Vita-Salute San Raffaele University; Department of Medical Oncology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy. Electronic address: necchi.andrea@hsr.it. 2. Department of Urology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy. 3. Department of Medical Oncology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy. 4. Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 5. Department of Pathology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy. 6. Vita-Salute San Raffaele University; Department of Urology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy. 7. Foundation Medicine Inc., Cambridge, MA; Upstate Medical University, New York, NY. 8. Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Abstract
INTRODUCTION: Advances in neoadjuvant therapy for patients with localized, nonmetastatic, upper tract urothelial carcinoma (UTUC) is needed. 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.
INTRODUCTION: Advances in neoadjuvant therapy for patients with localized, nonmetastatic, upper tract urothelial carcinoma (UTUC) is needed. 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.
Authors: Gianluigi Califano; Idir Ouzaid; Paul Laine-Caroff; Arthur Peyrottes; Claudia Collà Ruvolo; Benjamin Pradère; Vincent Elalouf; Vincent Misrai; Jean-François Hermieu; Shahrokh F Shariat; Evanguelos Xylinas Journal: Curr Oncol Date: 2022-01-29 Impact factor: 3.677