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.

Autor:	Hahn NM; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA. Electronic address: nhahn4@jhmi.edu., O'Donnell MA; University of Iowa Carver College of Medicine, Iowa City, IA, USA., Efstathiou JA; Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Zahurak M; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA., Rosner GL; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA., Smith J; Hoosier Cancer Research Network, Indianapolis, IN, USA., Kates MR; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA., Bivalacqua TJ; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA; Division of Urology and Urologic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Tran PT; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA; Department of Radiation Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA., Song DY; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA; Department of Radiation Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Baras AS; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Matoso A; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Choi W; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA., Smith KN; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; Johns Hopkins Bloomberg Kimmel Institute for Cancer Immunotherapy, Baltimore, MD, USA., Pardoll DM; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; Johns Hopkins Bloomberg Kimmel Institute for Cancer Immunotherapy, Baltimore, MD, USA., Marchionni L; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; Johns Hopkins University School of Medicine, Center for Computational Genomics, Baltimore, MD, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA., McGuire B; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA., Grace Phelan M; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA., Johnson BA 3rd; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA., O'Neal T; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA., McConkey DJ; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; The James Buchanan Brady Urological Institute, Baltimore, MD, USA., Rose TL; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA; Division of Medical Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA., Bjurlin M; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA; Department of Urology, University of North Carolina, Chapel Hill, NC, USA., Lim EA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA; Spectrum Health Medical Group, Grand Rapids, MI, USA., Drake CG; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA; Janssen Research and Development, Springhouse, PA, USA., McKiernan JM; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA; Department of Urology, Columbia University, New York, NY, USA., Deutsch I; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA; Department of Radiation Oncology, Columbia University, New York, NY, USA., Anderson CB; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA; Department of Urology, Columbia University, New York, NY, USA., Lamm DL; BCG Oncology, Phoenix, AZ, USA., Geynisman DM; Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., Plimack ER; Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., Hallman MA; Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., Horwitz EM; Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., Al-Saleem E; Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA., Chen DYT; Department of Urology, Fox Chase Cancer Center, Philadelphia, PA, USA., Greenberg RE; Department of Urology, Fox Chase Cancer Center, Philadelphia, PA, USA., Kutikov A; Department of Urology, Fox Chase Cancer Center, Philadelphia, PA, USA., Guo G; Department of Radiation Oncology, Indiana University Simon Cancer Center, Indianapolis, IN, USA; University Hospitals Cleveland Medical Center, Cleveland, OH, USA., Masterson TA; Department of Urology, Indiana University Simon Cancer Center, Indianapolis, IN, USA., Adra N; Division of Hematology and Oncology, Indiana University Simon Cancer Center, Indianapolis, IN, USA., Kaimakliotis HZ; Department of Urology, Indiana University Simon Cancer Center, Indianapolis, IN, USA.
Jazyk:	angličtina
Zdroj:	European urology [Eur Urol] 2023 Jun; Vol. 83 (6), pp. 486-494. Date of Electronic Publication: 2023 Jan 28.
DOI:	10.1016/j.eururo.2023.01.017
Abstrakt:	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 × 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 × 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. (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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