PMID- 36803840
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20240111
IS  - 2588-9311 (Electronic)
IS  - 2588-9311 (Linking)
VI  - 6
IP  - 3
DP  - 2023 Jun
TI  - A Phase 1b/2 Study of Atezolizumab with or Without Bacille Calmette-Guerin in 
      Patients with High-risk Non-muscle-invasive Bladder Cancer.
PG  - 313-320
LID - S2588-9311(23)00032-9 [pii]
LID - 10.1016/j.euo.2023.01.013 [doi]
AB  - BACKGROUND: Bacille Calmette-Guerin (BCG) is the standard therapy after 
      transurethral resection of bladder tumour for high-risk non-muscle-invasive 
      bladder cancer (NMIBC). However, post-BCG recurrence/progression occurs 
      frequently, and noncystectomy options are limited. OBJECTIVE: To evaluate the 
      safety and clinical activity of atezolizumab +/- BCG in high-risk BCG-unresponsive 
      NMIBC. DESIGN, SETTING, AND PARTICIPANTS: This phase 1b/2 GU-123 study 
      (NCT02792192) treated patients with BCG-unresponsive NMIBC who had carcinoma in 
      situ with atezolizumab +/- BCG. INTERVENTION: Patients in cohorts 1A and 1B 
      received atezolizumab 1200 mg IV q3w for </=96 wk. Those in cohort 1B also received 
      standard BCG induction (six weekly doses) and maintenance courses (three doses 
      weekly starting at month 3) with optional maintenance at 6, 12, 18, 24, and 30 
      mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Coprimary endpoints were 
      safety and 6-mo complete response (CR) rate. Secondary endpoints included 3-mo CR 
      rate and duration of CR; 95% confidence intervals were calculated using the 
      Clopper-Pearson method. RESULTS AND LIMITATIONS: At data cut-off (September 29, 
      2020), 24 patients were enrolled (cohort 1A, n = 12; cohort 1B, n = 12), and the 
      recommended BCG dose was 50 mg in cohort 1B. Four patients (33%) had adverse 
      events (AEs) leading to BCG dose modification/interruption. Three patients (25%) 
      in cohort 1A reported atezolizumab-related grade 3 AEs; cohort 1B had no 
      atezolizumab- or BCG-related grade >/=3 AEs. No grade 4/5 AEs were reported. The 
      6-mo CR rate was 33% in cohort 1A (median duration of CR, 6.8 mo) and 42% in 
      cohort 1B (median duration of CR, not reached [>/=12 mo]). These results are 
      limited by the small sample size of GU-123. CONCLUSIONS: In this first report of 
      the atezolizumab-BCG combination in NMIBC, atezolizumab +/- BCG was well tolerated, 
      with no new safety signals or treatment-related deaths. Preliminary results 
      suggested clinically meaningful activity; the combination favoured a longer 
      duration of response. PATIENT SUMMARY: We studied atezolizumab with and without 
      bacille Calmette-Guerin (BCG) to determine whether this combination was safe and 
      had clinical activity in patients with high-risk noninvasive bladder cancer 
      (high-grade bladder tumours that affect the outermost lining of the bladder wall) 
      that has previously been treated with BCG and is still present or occurred again. 
      Our results suggest that atezolizumab with or without BCG was generally safe and 
      could be used to treat patients unresponsive to BCG.
CI  - Copyright (c) 2023 European Association of Urology. Published by Elsevier B.V. All 
      rights reserved.
FAU - Inman, Brant A
AU  - Inman BA
AD  - Duke Cancer Institute, Duke University, Durham, NC, USA. Electronic address: 
      brant.inman@duke.edu.
FAU - Hahn, Noah M
AU  - Hahn NM
AD  - Department of Oncology, Johns Hopkins Greenberg Bladder Cancer Institute, Johns 
      Hopkins University School of Medicine, Baltimore, MD, USA; Department of Urology, 
      Johns Hopkins Greenberg Bladder Cancer Institute, Johns Hopkins University School 
      of Medicine, Baltimore, MD, USA.
FAU - Stratton, Kelly
AU  - Stratton K
AD  - Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma 
      City, OK, USA.
FAU - Kopp, Ryan
AU  - Kopp R
AD  - Department of Urology, Oregon Health & Science University, Portland, OR, USA; VA 
      Portland Healthcare System, Portland, OR, USA.
FAU - Sankin, Alex
AU  - Sankin A
AD  - Department of Urology, Montefiore Medical Center, Bronx, NY, USA.
FAU - Skinner, Eila
AU  - Skinner E
AD  - Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
FAU - Pohar, Kamal
AU  - Pohar K
AD  - Department of Urology, Ohio State University, Columbus, OH, USA.
FAU - Gartrell, Benjamin A
AU  - Gartrell BA
AD  - Department of Oncology, Montefiore Medical Center, Bronx, NY, USA.
FAU - Pham, Song
AU  - Pham S
AD  - Genentech Inc, South San Francisco, CA, USA.
FAU - Rishipathak, Deepali
AU  - Rishipathak D
AD  - Genentech Inc, South San Francisco, CA, USA.
FAU - Mariathasan, Sanjeev
AU  - Mariathasan S
AD  - Genentech Inc, South San Francisco, CA, USA.
FAU - Davarpanah, Nicole
AU  - Davarpanah N
AD  - Genentech Inc, South San Francisco, CA, USA.
FAU - Carter, Corey
AU  - Carter C
AD  - Genentech Inc, South San Francisco, CA, USA.
FAU - Steinberg, Gary D
AU  - Steinberg GD
AD  - Goldstein Bladder Cancer Program, NYU Langone Health, New York, NY, USA; 
      Department of Urology, New York University School of Medicine, New York, NY, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02792192
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230215
PL  - Netherlands
TA  - Eur Urol Oncol
JT  - European urology oncology
JID - 101724904
RN  - 0 (BCG Vaccine)
SB  - IM
CIN - Eur Urol Oncol. 2023 Jun;6(3):321-322. doi: 10.1016/j.euo.2023.03.006. PMID: 
      37045706
MH  - Humans
MH  - BCG Vaccine/therapeutic use
MH  - *Non-Muscle Invasive Bladder Neoplasms
MH  - *Urinary Bladder Neoplasms/pathology
MH  - Administration, Intravesical
OTO - NOTNLM
OT  - Atezolizumab
OT  - BCG unresponsive
OT  - Bacille Calmette-Guerin
OT  - Carcinoma in situ
OT  - Non-muscle-invasive bladder cancer
EDAT- 2023/02/22 06:00
MHDA- 2023/06/19 13:08
CRDT- 2023/02/21 18:23
PHST- 2022/08/15 00:00 [received]
PHST- 2022/12/02 00:00 [revised]
PHST- 2023/01/20 00:00 [accepted]
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/02/22 06:00 [pubmed]
PHST- 2023/02/21 18:23 [entrez]
AID - S2588-9311(23)00032-9 [pii]
AID - 10.1016/j.euo.2023.01.013 [doi]
PST - ppublish
SO  - Eur Urol Oncol. 2023 Jun;6(3):313-320. doi: 10.1016/j.euo.2023.01.013. Epub 2023 
      Feb 15.