A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study

被引：33

作者：

Hahn, Noah M. ^{[1
,3
]}

O'Donnell, Michael A. ^{[4
]}

Efstathiou, Jason A. ^{[5
,6
]}

Zahurak, Marianna ^{[1
]}

Rosner, Gary L. ^{[1
]}

Smith, Jeff ^{[7
]}

Kates, Max R. ^{[1
,2
,3
]}

Bivalacqua, Trinity J. ^{[1
,2
,3
,8
]}

Tran, Phuoc T. ^{[1
,2
,3
,9
,10
]}

Song, Daniel Y. ^{[1
,2
,3
,9
]}

Baras, Alex S. ^{[1
,2
,3
,11
]}

Matoso, Andres ^{[1
,2
,3
,11
]}

Choi, Woonyoung ^{[1
,2
,3
]}

Smitha, Kellie N. ^{[1
,2
,12
]}

Pardoll, Drew M. ^{[1
,2
,12
]}

Marchionni, Luigi ^{[1
,2
,13
,14
]}

McGuire, Bridget ^{[1
,2
,3
]}

Phelan, Mary Grace ^{[1
,2
,3
]}

Johnson, Burles A. ^{[1
,2
,3
]}

O'Neal, Tanya ^{[1
]}

McConkey, David J. ^{[1
]}

Roseo, Tracy L. ^{[1
,2
,3
,15
,16
]}

Bjurlin, Marc ^{[15
,17
]}

Lim, Emerson A. ^{[18
,19
]}

Drake, Charles G. ^{[18
,20
]}

McKiernan, James M. ^{[18
,21
]}

Deutschr, Israel ^{[18
,22
]}

Andersonr, Christopher B. ^{[18
,21
]}

Lamm, Donald L. ^{[23
]}

Geynisman, Daniel M. ^{[24
]}

Plimack, Elizabeth R. ^{[24
]}

Hallmany, Mark A. ^{[25
]}

Horwitzy, Eric M. ^{[25
]}

Al-Saleem, Essel ^{[26
]}

Chen, David Y. T. ^{[27
]}

Greenberg, Richard E. ^{[27
]}

Kutikov, Alexander ^{[27
]}

Guo, Gordon ^{[28
,29
]}

Masterson, Timothy A. ^{[30
]}

Adra, Nabil ^{[31
]}

Kaimakliotis, Hristos Z.

机构：

[1] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[2] Johns Hopkins Greenberg Bladder Canc Inst, Baltimore, MD USA

[3] James Buchanan Brady Urol Inst, Baltimore, MD USA

[4] Univ Iowa, Carver Coll Med, Iowa City, IA USA

[5] Massachusetts Gen Hosp, Boston, MA USA

[6] Harvard Med Sch, Boston, MA USA

[7] Hoosier Canc Res Network, Indianapolis, IN USA

[8] Univ Penn, Div Urol & Urol Surg, Dept Surg, Perelman Sch Med, Philadelphia, PA USA

[9] Johns Hopkins Sch Med, Dept Radiat Oncol, Baltimore, MD USA

[10] Univ Maryland, Dept Radiat Oncol, Sch Med, Baltimore, MD USA

[11] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA

[12] Johns Hopkins Bloomberg Kimmel Inst Canc Immunoth, Baltimore, MD USA

[13] Johns Hopkins Univ, Ctr Computat Genom, Sch Med, Baltimore, MD USA

[14] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA

[15] Univ North Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[16] Univ North Carolina, Div Med Oncol, Dept Med, Chapel Hill, NC USA

[17] Univ North Carolina, Dept Urol, Chapel Hill, NC USA

[18] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA

[19] Spectrum Hlth Med Grp, Grand Rapids, MI USA

[20] Janssen Res & Dev, Spring House, PA USA

[21] Columbia Univ, Dept Urol, New York, NY USA

[22] Columbia Univ, Dept Radiat Oncol, New York, NY USA

[23] BCG Oncol, Phoenix, AZ USA

[24] Fox Chase Canc Ctr, Dept Hematol & Oncol, Philadelphia, PA USA

[25] Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA USA

[26] Dept Pathol, Fox Chase Canc Ctr, Philadelphia, PA USA

[27] Dept Urol, Fox Chase Canc Ctr, Philadelphia, PA USA

[28] Indiana Univ Simon Canc Ctr, Dept Radiat Oncol, Indianapolis, IN USA

[29] Univ Hosp Cleveland Med Ctr, Cleveland, OH USA

[30] Indiana Univ Simon Canc Ctr, Dept Urol, Indianapolis, IN USA

[31] Indiana Univ Simon Canc Ctr, Div Hematol & Oncol, Indianapolis, IN USA

来源：

EUROPEAN UROLOGY | 2023年 / 83卷 / 06期

关键词：

Bacillus Calmette-Guerin; Bacillus Calmette-Guerin unresponsive; Bladder cancer; Clinical trial; Durvalumab; Non-muscle invasive; PD-L1; Radiation; Urothelial carcinoma; UROTHELIAL CARCINOMA; CLINICAL-TRIALS; OPEN-LABEL; IMMUNOTHERAPY; CHEMOTHERAPY; MULTICENTER; EXPRESSION; SURVIVAL; OUTCOMES;

D O I：

10.1016/j.eururo.2023.01.017

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients. Objective: To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT). Design, setting, and participants: A multicenter phase 1 trial was conducted at community and academic sites. Intervention: Patients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy x 3 in cycle 1 only). Outcome measurements and statistical analysis: Post-treatment cystoscopy and urine cytology were performed at 3 and 6 -mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates. Results and limitations: Twenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions x 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients. Conclusions: D combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches. Patient summary: Durvalumab combination therapy can be safely administered to non-muscle-invasive bladder cancer patients with the goal of increasing durable response rates. (c) 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

引用

页码：486 / 494

页数：9

共 34 条

[1] Durvalumab in cancer medicine: a comprehensive review [J].

Alvarez-Argote, Juliana ;

Dasanu, Constantin A. .

EXPERT OPINION ON BIOLOGICAL THERAPY, 2019, 19 (09) :927-935

[2]

[Anonymous], 2017, COMMON TERMINOLOGY C, P155

[3] Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guerin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer [J].

Arends, Tom J. H. ;

Nativ, Ofer ;

Maffezzini, Massimo ;

de Cobelli, Ottavio ;

Canepa, Giorgio ;

Verweij, Fabrizio ;

Moskovitz, Boaz ;

van der Heijden, Antoine G. ;

Witjes, J. Alfred .

EUROPEAN UROLOGY, 2016, 69 (06) :1046-1052

[4] EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016 [J].

Babjuk, Marko ;

Boehle, Andreas ;

Burger, Maximilian ;

Capoun, Otakar ;

Cohen, Daniel ;

Comperat, Eva M. ;

Hernandez, Virginia ;

Kaasinen, Eero ;

Palou, Joan ;

Roupret, Morgan ;

van Rhijn, Bas W. G. ;

Shariat, Shahrokh F. ;

Soukup, Viktor ;

Sylvester, Richard J. ;

Zigeuner, Richard .

EUROPEAN UROLOGY, 2017, 71 (03) :447-461

[5] Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study [J].

Balar, Arjun, V ;

Kamat, Ashish M. ;

Kulkarni, Girish S. ;

Uchio, Edward M. ;

Boormans, Joost L. ;

Roumiguie, Mathieu ;

Krieger, Laurence E. M. ;

Singer, Eric A. ;

Bajorin, Dean F. ;

Grivas, Petros ;

Seo, Ho Kyung ;

Nishiyama, Hiroyuki ;

Konety, Badrinath R. ;

Li, Haojie ;

Nam, Kijoeng ;

Kapadia, Ekta ;

Frenkl, Tara ;

de Wit, Ronald .

LANCET ONCOLOGY, 2021, 22 (07) :919-930

[6] Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial [J].

Boorjian, Stephen A. ;

Alemozaffar, Mehrdad ;

Konety, Badrinath R. ;

Shore, Neal D. ;

Gomella, Leonard G. ;

Kamat, Ashish M. ;

Bivalacqua, Trinity J. ;

Montgomery, Jeffrey S. ;

Lerner, Seth P. ;

Busby, Joseph E. ;

Poch, Michael ;

Crispen, Paul L. ;

Steinberg, Gary D. ;

Schuckman, Anne K. ;

Downs, Tracy M. ;

Svatek, Robert S. ;

Mashni, Joseph, Jr. ;

Lane, Brian R. ;

Guzzo, Thomas J. ;

Bratslavsky, Gennady ;

Karsh, Lawrence I. ;

Woods, Michael E. ;

Brown, Gordon ;

Canter, Daniel ;

Luchey, Adam ;

Lotan, Yair ;

Krupski, Tracey ;

Inman, Brant A. ;

Williams, Michael B. ;

Cookson, Michael S. ;

Keegan, Kirk A. ;

Andriole, Gerald L., Jr. ;

Sankin, Alexander I. ;

Boyd, Alan ;

O'Donnell, Michael A. ;

Sawutz, David ;

Philipson, Richard ;

Coll, Ruth ;

Narayan, Vikram M. ;

Treasure, F. Peter ;

Yla-Herttuala, Seppo ;

Parker, Nigel R. ;

Dinney, Colin P. N. .

LANCET ONCOLOGY, 2021, 22 (01) :107-117

[7] High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients [J].

Breyer, Johannes ;

Wirtz, Ralph M. ;

Otto, Wolfgang ;

Erben, Philipp ;

Worst, Thomas S. ;

Stoehr, Robert ;

Eckstein, Markus ;

Denzinger, Stefan ;

Burger, Maximilian ;

Hartmann, Arndt .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2018, 67 (03) :403-412

[8]

Chamie K, 2022, J CLIN ONCOL, V40

[9] Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline [J].

Chang, Sam S. ;

Bochner, Bernard H. ;

Chou, Roger ;

Dreicer, Robert ;

Kamat, Ashish M. ;

Lerner, Seth P. ;

Lotan, Yair ;

Meeks, Joshua J. ;

Michalski, Jeff M. ;

Morgan, Todd M. ;

Quale, Diane Z. ;

Rosenberg, Jonathan E. ;

Zietman, Anthony L. ;

Holzbeierlein, Jeffrey M. .

JOURNAL OF UROLOGY, 2017, 198 (03) :552-559

[10] Bladder Preservation With Twice-a-Day Radiation Plus Fluorouracil/Cisplatin or Once Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer: NRG/RTOG 0712A Randomized Phase II Trial [J].

Coen, John J. ;

Zhang, Peixin ;

Saylor, Philip J. ;

Lee, Cheryl T. ;

Wu, Chin-Lee ;

Parker, William ;

Lautenschlaeger, Timothy ;

Zietman, Anthony L. ;

Efstathiou, Jason A. ;

Jani, Ashesh B. ;

Kucuk, Omer ;

Souhami, Luis ;

Rodgers, Joseph P. ;

Sandler, Howard M. ;

Shipley, William U. .

JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (01) :44-+

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