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

Volumn 36, Issue 34, 2018, Pages 3353-3360

  Necchi, Andrea ^a   Anichini, Andrea ^a   Raggi, Daniele ^a   Briganti, Alberto ^b   Massa, Simona ^a   Lucianò, Roberta ^b   Colecchia, Maurizio ^a   Giannatempo, Patrizia ^a   Mortarini, Roberta ^a   Bianchi, Marco ^b   Farè, Elena ^a   Monopoli, Francesco ^a   Colombo, Renzo ^b   Gallina, Andrea ^b   Salonia, Andrea ^b   Messina, Antonella ^a   Ali, Siraj M ^c   Madison, Russell ^c   Ross, Jeffrey S ^c,d   Chung, Jon H ^c   Salvioni, Roberto ^a   Mariani, Luigi ^a   Montorsi, Francesco ^b   more..

^a NATIONAL CANCER INSTITUTE   (Italy)

^b VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^c FOUNDATION MEDICINE   (United States)

^d SUNY UPSTATE MEDICAL UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; CISPLATIN; PEMBROLIZUMAB; PROGRAMMED DEATH 1 LIGAND 1; MONOCLONAL ANTIBODY;

ADULT; AGED; ARTICLE; CANCER ADJUVANT THERAPY; CANCER IMMUNOTHERAPY; CANCER PATIENT; CANCER STAGING; CLINICAL ARTICLE; CORTICOSTEROID THERAPY; CYSTECTOMY; DRUG EFFICACY; FEMALE; FEVER; GENE EXPRESSION ASSAY; HUMAN; INTENTION TO TREAT ANALYSIS; MALE; MULTIPLE CYCLE TREATMENT; MUSCLE INVASIVE BLADDER CANCER; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL; POSTOPERATIVE COMPLICATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PRURITUS; SEPSIS; TRANSITIONAL CELL CARCINOMA; TREATMENT FAILURE; TREATMENT RESPONSE; XEROSTOMIA; BLADDER TUMOR; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DOSE RESPONSE; DRUG ADMINISTRATION; ITALY; MIDDLE AGED; MORTALITY; MULTICENTER STUDY; MULTIVARIATE ANALYSIS; NEOADJUVANT THERAPY; PATHOLOGY; PROCEDURES; PROGNOSIS; RISK ASSESSMENT; STATISTICAL MODEL; SURVIVAL ANALYSIS; TUMOR INVASION; UNIVERSITY HOSPITAL;

ACADEMIC MEDICAL CENTERS; ADULT; AGED; ANTIBODIES, MONOCLONAL, HUMANIZED; CARCINOMA, TRANSITIONAL CELL; CYSTECTOMY; DISEASE-FREE SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; ITALY; LOGISTIC MODELS; MALE; MIDDLE AGED; MULTIVARIATE ANALYSIS; NEOADJUVANT THERAPY; NEOPLASM INVASIVENESS; NEOPLASM STAGING; PROGNOSIS; RISK ASSESSMENT; SURVIVAL ANALYSIS; URINARY BLADDER NEOPLASMS;

EID: 85057297203     PISSN: 0732183X     EISSN: 15277755     Source Type: Journal    
DOI: 10.1200/JCO.18.01148     Document Type: Article

References (31)

1. Alfred Witjes J, Lebret T, Compérat EM, et al: Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol 71:462-475, 2017
2. Burger M, Mulders P, Witjes W: Use of neoadjuvant chemotherapy for muscle-invasive bladder cancer is low among major European centres: Results of a feasibility questionnaire. Eur Urol 61:1070-1071, 2012
3. Galsky MD, Hahn NM, Rosenberg J, et al: Treatment of patients with metastatic urothelial cancer “unfit” for cisplatin-based chemotherapy. J Clin Oncol 29:2432-2438, 2011
4. Gore JL, Lai J, Setodji CM, et al: Mortality increases when radical cystectomy is delayed more than 12 weeks: Results from a Surveillance, Epidemiology, and End Results-Medicare analysis. Cancer 115: 988-996, 2009
5. Bhindi B, Frank I, Mason RJ, et al: Oncologic outcomes for patients with residual cancer at cystectomy following neoadjuvant chemotherapy: A pathologic stage-matched analysis. Eur Urol 72: 660-664, 2017
6. Stein JP, Lieskovsky G, Cote R, et al: Radical cystectomy in the treatment of invasive bladder cancer: Long-term results in 1,054 patients. J Clin Oncol 19:666-675, 2001
7. Chism DD, Woods ME, Milowsky MI: Neoadjuvant paradigm for accelerated drug development: An ideal model in bladder cancer. Oncologist 18:933-940, 2013
8. Sonpavde G, Goldman BH, Speights VO, et al: Quality of pathologic response and surgery correlate with survival for patients with completely resected bladder cancer after neoadjuvant chemotherapy. Cancer 115:4104-4109, 2009
9. Bellmunt J, de Wit R, Vaughn DJ, et al: Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 376:1015-1026, 2017
10. Balar AV, Castellano D, O’Donnell PH, et al: First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): A multicentre, single-arm, phase 2 study. Lancet Oncol 18:1483-1492, 2017
11. Powles T, Gschwend JE, Loriot Y, et al: Pembrolizumab ± chemotherapy versus chemotherapy in advanced urothelial cancer: Phase 3 Keynote-361 trial. Ann Oncol 28:v295-v329, 2017 (suppl 5)
12. Forde PM, Chaft JE, Smith KN, et al: Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med 378:1976-1986, 2018
13. Parekh DJ, Reis IM, Castle EP, et al: Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): An open-label, randomised, phase 3, non-inferiority trial. Lancet 391:2525-2536, 2018
14. Frampton GM, Fichtenholtz A, Otto GA, et al: Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol 31:1023-1031, 2013
15. Chalmers ZR, Connelly CF, Fabrizio D, et al: Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 9:34, 2017
16. Ayers M, Lunceford J, Nebozhyn M, et al: IFN-ɣ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest 127: 2930-2940, 2017
17. Perotti V, Baldassari P, Molla A, et al: NFATc2 is an intrinsic regulator of melanoma dedifferentiation. Oncogene 35:2862-2872, 2016
18. Hugo W, Zaretsky JM, Sun L, et al: Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell 165:35-44, 2016
19. [Erratum: Cell 168:542, 2017]
20. Schultz JR, Nichol FR, Elfring GL, et al: Multiple-stage procedures for drug screening. Biometrics 29:293-300, 1973
21. Powles T, Rodriguez-Vida A, Duran I, et al: A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in muscle invasive bladder cancer (ABACUS). J Clin Oncol 36, 2018 (suppl; abstr 4506)
22. Rosenberg JE, Hoffman-Censits J, Powles T, et al: Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet 387:1909-1920, 2016
23. Riaz N, Havel JJ, Makarov V, et al: Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell 171:934-949.e15, 2017
24. Teo MY, Seier K, Ostrovnaya I, et al: Alterations in DNA damage response and repair genes as potential marker of clinical benefit from PD-1/PD-L1 blockade in advanced urothelial cancers. J Clin Oncol 36:1685-1694, 2018
25. Plimack ER, Dunbrack RL, Brennan TA, et al: Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Eur Urol 68:959-967, 2015
26. Iyer G, Balar AV, Milowsky MI, et al: Multi-center prospective phase II trial of neoadjuvant dose-dense gemcitabine plus cisplatin in patients with muscle-invasive bladder cancer. J Clin Oncol 36: 1949-1956, 2018
27. Bratslavsky G, Gay LM, Sokol E, et al: PBRM1 mutation and immunotherapy efficacy: A comprehensive genomic profiling (CGP) assessment. J Clin Oncol 36, 2018 (suppl; abstr 12091)
28. Miao D, Margolis CA, Gao W, et al: Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science 359: 801-806, 2018
29. Sweis RF, Spranger S, Bao R, et al: Molecular drivers of the non-T-cell-inflamed tumor microenvironment in urothelial bladder cancer. Cancer Immunol Res 4:563-568, 2016
30. Panebianco V, Narumi Y, Altun E, et al: Multiparametric magnetic resonance imaging for bladder cancer: Development of VI-RADS (Vesical Imaging-Reporting And Data System). Eur Urol 74:294-306, 2018
31. Bandini M, Briganti A, Plimack ER, et al: Modeling 1-year relapse-free survival after neoadjuvant chemotherapy and radical cystectomy in patients with clinical T2-4N0M0 urothelial bladder carcinoma: Endpoints for phase 2 trials. Eur Urol Oncol 10.1016/j.euo.2018.08.009 [epub ahead of print on August 9, 2018]