Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): An open-label, single-arm, phase II study

A Necchi, A Anichini, D Raggi, A Briganti, S Massa, R Lucianò, M Colecchia, P Giannatempo, R Mortarini, M Bianchi, Elena Farè, F Monopoli, R Colombo, A Gallina, A Salonia, A Messina, SM Ali, R Madison, JS Ross, JH ChungR Salvioni, L Mariani, F Montorsi

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Abstract

Purpose To determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used. Patients and Methods In the PURE-01 study, patients had a predominant urothelial carcinoma histology and clinical (c) T≤3bN0 stage tumor. They received three cycles of pembrolizumab 200 mg every 3 weeks before RC. The primary end point in the intention-to-treat population was pathologic complete response (pT0). Biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay), genomic sequencing (FoundationONE assay), and an immune gene expression assay. Results Fifty patients were enrolled from February 2017 to March 2018. Twenty-seven patients (54%) had cT3 tumor, 21 (42%) cT2 tumor, and two (4%) cT2-3N1 tumor. One patient (2%) experienced a grade 3 transaminase increase and discontinued pembrolizumab. All patients underwent RC; there were 21 patients with pT0 (42%; 95% CI, 28.2% to 56.8%). As a secondary end point, downstaging to pT,
Original languageEnglish
Pages (from-to)3353-3360
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number34
DOIs
Publication statusPublished - 2018

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Neoadjuvant Therapy
Cystectomy
Urinary Bladder
Carcinoma
Muscles
Neoplasms
Transaminases
pembrolizumab
Immunotherapy
Cisplatin
Histology
Biomarkers
Ligands
Gene Expression
Drug Therapy
Population

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Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): An open-label, single-arm, phase II study. / Necchi, A; Anichini, A; Raggi, D; Briganti, A; Massa, S; Lucianò, R; Colecchia, M; Giannatempo, P; Mortarini, R; Bianchi, M; Farè, Elena; Monopoli, F; Colombo, R; Gallina, A; Salonia, A; Messina, A; Ali, SM; Madison, R; Ross, JS; Chung, JH; Salvioni, R; Mariani, L; Montorsi, F.

In: Journal of Clinical Oncology, Vol. 36, No. 34, 2018, p. 3353-3360.

Research output: Contribution to journalArticle

Necchi, A, Anichini, A, Raggi, D, Briganti, A, Massa, S, Lucianò, R, Colecchia, M, Giannatempo, P, Mortarini, R, Bianchi, M, Farè, E, Monopoli, F, Colombo, R, Gallina, A, Salonia, A, Messina, A, Ali, SM, Madison, R, Ross, JS, Chung, JH, Salvioni, R, Mariani, L & Montorsi, F 2018, 'Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): An open-label, single-arm, phase II study', Journal of Clinical Oncology, vol. 36, no. 34, pp. 3353-3360. https://doi.org/10.1200/JCO.18.01148
Necchi, A ; Anichini, A ; Raggi, D ; Briganti, A ; Massa, S ; Lucianò, R ; Colecchia, M ; Giannatempo, P ; Mortarini, R ; Bianchi, M ; Farè, Elena ; Monopoli, F ; Colombo, R ; Gallina, A ; Salonia, A ; Messina, A ; Ali, SM ; Madison, R ; Ross, JS ; Chung, JH ; Salvioni, R ; Mariani, L ; Montorsi, F. / Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): An open-label, single-arm, phase II study. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 34. pp. 3353-3360.
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title = "Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): An open-label, single-arm, phase II study",
abstract = "Purpose To determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used. Patients and Methods In the PURE-01 study, patients had a predominant urothelial carcinoma histology and clinical (c) T≤3bN0 stage tumor. They received three cycles of pembrolizumab 200 mg every 3 weeks before RC. The primary end point in the intention-to-treat population was pathologic complete response (pT0). Biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay), genomic sequencing (FoundationONE assay), and an immune gene expression assay. Results Fifty patients were enrolled from February 2017 to March 2018. Twenty-seven patients (54{\%}) had cT3 tumor, 21 (42{\%}) cT2 tumor, and two (4{\%}) cT2-3N1 tumor. One patient (2{\%}) experienced a grade 3 transaminase increase and discontinued pembrolizumab. All patients underwent RC; there were 21 patients with pT0 (42{\%}; 95{\%} CI, 28.2{\%} to 56.8{\%}). As a secondary end point, downstaging to pT,",
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T1 - Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): An open-label, single-arm, phase II study

AU - Necchi, A

AU - Anichini, A

AU - Raggi, D

AU - Briganti, A

AU - Massa, S

AU - Lucianò, R

AU - Colecchia, M

AU - Giannatempo, P

AU - Mortarini, R

AU - Bianchi, M

AU - Farè, Elena

AU - Monopoli, F

AU - Colombo, R

AU - Gallina, A

AU - Salonia, A

AU - Messina, A

AU - Ali, SM

AU - Madison, R

AU - Ross, JS

AU - Chung, JH

AU - Salvioni, R

AU - Mariani, L

AU - Montorsi, F

PY - 2018

Y1 - 2018

N2 - Purpose To determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used. Patients and Methods In the PURE-01 study, patients had a predominant urothelial carcinoma histology and clinical (c) T≤3bN0 stage tumor. They received three cycles of pembrolizumab 200 mg every 3 weeks before RC. The primary end point in the intention-to-treat population was pathologic complete response (pT0). Biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay), genomic sequencing (FoundationONE assay), and an immune gene expression assay. Results Fifty patients were enrolled from February 2017 to March 2018. Twenty-seven patients (54%) had cT3 tumor, 21 (42%) cT2 tumor, and two (4%) cT2-3N1 tumor. One patient (2%) experienced a grade 3 transaminase increase and discontinued pembrolizumab. All patients underwent RC; there were 21 patients with pT0 (42%; 95% CI, 28.2% to 56.8%). As a secondary end point, downstaging to pT,

AB - Purpose To determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used. Patients and Methods In the PURE-01 study, patients had a predominant urothelial carcinoma histology and clinical (c) T≤3bN0 stage tumor. They received three cycles of pembrolizumab 200 mg every 3 weeks before RC. The primary end point in the intention-to-treat population was pathologic complete response (pT0). Biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay), genomic sequencing (FoundationONE assay), and an immune gene expression assay. Results Fifty patients were enrolled from February 2017 to March 2018. Twenty-seven patients (54%) had cT3 tumor, 21 (42%) cT2 tumor, and two (4%) cT2-3N1 tumor. One patient (2%) experienced a grade 3 transaminase increase and discontinued pembrolizumab. All patients underwent RC; there were 21 patients with pT0 (42%; 95% CI, 28.2% to 56.8%). As a secondary end point, downstaging to pT,

U2 - 10.1200/JCO.18.01148

DO - 10.1200/JCO.18.01148

M3 - Article

VL - 36

SP - 3353

EP - 3360

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 34

ER -