Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer

被引：29

作者：

Powles, Thomas ^{[1
]}

Catto, James W. F. ^{[2
,3
]}

Galsky, Matthew D. ^{[5
]}

Al-Ahmadie, Hikmat ^{[6
]}

Meeks, Joshua J. ^{[8
,9
]}

Nishiyama, Hiroyuki ^{[10
]}

Vu, Toan Quang ^{[11
]}

Antonuzzo, Lorenzo ^{[12
,13
]}

Wiechno, Pawel ^{[14
]}

Atduev, Vagif ^{[15
]}

Kann, Ariel G. ^{[16
]}

Kim, Tae-Hwan ^{[17
]}

Suarez, Cristina ^{[18
]}

Chang, Chao-Hsiang ^{[19
,20
]}

Roghmann, Florian ^{[21
]}

Ozguroglu, Mustafa ^{[22
]}

Eigl, Bernhard J. ^{[23
]}

Oliveira, Niara ^{[24
,25
]}

Buchler, Tomas ^{[26
,27
]}

Gadot, Moran ^{[28
,29
]}

Zakharia, Yousef ^{[30
]}

Armstrong, Jon ^{[4
]}

Gupta, Ashok ^{[7
]}

Hois, Stephan ^{[31
]}

van der Heijden, Michiel S. ^{[32
]}

机构：

[1] Queen Mary Univ London, Barts Hlth NHS Trust Biomed Res Ctr, Barts Canc Inst, London, England

[2] Univ Sheffield, Sch Med & Populat Hlth, Div Clin Med, Sheffield, S Yorkshire, England

[3] Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England

[4] AstraZeneca, Cambridge, England

[5] Icahn Sch Med Mt Sinai, Div Hematol & Med Oncol, Tisch Canc Inst, New York, NY 10029 USA

[6] Mem Sloan Kettering Canc Ctr, Dept Pathol & Lab Med, 1275 York Ave, New York, NY 10021 USA

[7] AstraZeneca, New York, NY USA

[8] Northwestern Univ, Dept Urol, Feinberg Sch Med, Chicago, IL 60611 USA

[9] Northwestern Univ, Dept Biochem, Feinberg Sch Med, Chicago, IL 60611 USA

[10] Univ Tsukuba, Tsukuba, Ibaraki, Japan

[11] Vietnam Natl Canc Hosp, Internal Med 3, Hanoi, Vietnam

[12] Univ Florence, Dept Expt & Clin Med, Florence, Italy

[13] Careggi Univ Hosp, Med Oncol Unit, Florence, Italy

[14] Maria Sklodowska Curie Natl Res Inst Oncol, Warsaw, Poland

[15] Fed Med Biol Agcy, Volga Dist Med Ctr, Nizhnii Novgorod, Russia

[16] Hosp Alemao Oswaldo Cruz, Sao Paulo, Brazil

[17] Kyungpook Natl Univ, Chilgok Hosp, Dept Urol, Daegu, South Korea

[18] Hosp Univ Vall Hebron, Med Oncol, Vall dHebron Inst, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain

[19] China Med Univ Hosp, Dept Urol, Taichung, Taiwan

[20] China Med Univ, Coll Chinese Med, Sch Med, Taichung, Taiwan

[21] Ruhr Univ Bochum, Marien Hosp Herne, Dept Urol, Herne, Germany

[22] Istanbul Univ Cerrahpasa, Cerrahpasa Med Sch, Istanbul, Turkiye

[23] BC Canc Vancouver, Vancouver, BC, Canada

[24] Mater Hosp Brisbane, Mater Misericordiae, Brisbane, Qld, Australia

[25] Univ Queensland, Mater Clin Unit, Sch Clin Med, Brisbane, Qld, Australia

[26] Charles Univ Prague, Fac Med 1, Dept Oncol, Prague, Czech Republic

[27] Thomayer Hosp, Prague, Czech Republic

[28] Sheba Med Ctr, Inst Oncol, Ramat Gan, Israel

[29] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel

[30] Univ Iowa Hosp & Clin, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA

[31] AstraZeneca, Gaithersburg, MD USA

[32] Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2024年 / 391卷 / 19期

关键词：

INVASIVE UROTHELIAL CARCINOMA; PHASE-II; NIVOLUMAB; PEMBROLIZUMAB;

D O I：

10.1056/NEJMoa2408154

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes. METHODS In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point. RESULTS In total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P = 0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group. CONCLUSIONS Perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone.

引用

页码：1773 / 1786

页数：14

共 30 条

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