Phase 2 Trial of Atezolizumab in Bacillus Calmette-Guérin-unresponsive High-risk Non-muscle-invasive Bladder Cancer: SWOG S1605.
Bacillus Calmette-Guérin–unresponsive
Bladder cancer
Immune checkpoint inhibitor
Journal
European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
09
03
2023
revised:
04
07
2023
accepted:
03
08
2023
medline:
1
12
2023
pubmed:
19
8
2023
entrez:
18
8
2023
Statut:
ppublish
Résumé
Although radical cystectomy (RC) is the standard of care for patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC), many patients are ineligible for surgery or elect bladder preservation. To evaluate the efficacy and safety of atezolizumab in BCG-unresponsive high-risk NMIBC. This was a single-arm phase 2 trial in patients with BCG-unresponsive high-risk NMIBC who were ineligible for or declined RC. Intravenous atezolizumab every 3 wk for 1 yr. The primary endpoint was the pathological complete response (CR) rate for patients with carcinoma in situ (CIS) determined via mandatory biopsy at 6 mo. Event-free survival (EFS) at 18 mo for patients with non-CIS tumors and treatment-related adverse events (TRAEs) were key secondary endpoints. Of 172 patients enrolled in the trial, 166 received at least one dose of atezolizumab (safety analysis) and 129 were eligible (efficacy analysis). Of the 74 patients with CIS, 20 (27%) experienced a CR at 6 mo. The median duration of response was 17 mo, and 56% (95% confidence interval [CI] 34-77%) of the responses were durable to at least 12 mo. The 18-mo actuarial EFS rate among 55 patients with Ta/T1 disease was 49% (90% CI 38-60%). Twelve of 129 eligible patients experienced progression to muscle-invasive or metastatic disease. Grade 3-5 TRAEs occurred in 26 patients (16%), including three treatment-related deaths. The study was limited by the small sample size and a high rate of patient ineligibility. The efficacy of atezolizumab observed among patients with BCG-unresponsive NMIBC is similar to results from similar trials with other agents, but did not meet the prespecified efficacy threshold. Modest efficacy needs to be balanced with a significant rate of TRAEs and the risk of disease progression when considering systemic immunotherapy in early-stage bladder cancer. We tested intravenous immunotherapy (atezolizumab) in patients with high-risk non-muscle-invasive bladder cancer that recurred after BCG (bacillus Calmette-Guérin) treatment. Although we found similar outcomes to previous trials, the benefit of this therapy is modest and needs to be carefully balanced with the significant risk of side effects. This trial is registered on ClinicalTrials.gov as NCT02844816.
Sections du résumé
BACKGROUND
BACKGROUND
Although radical cystectomy (RC) is the standard of care for patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC), many patients are ineligible for surgery or elect bladder preservation.
OBJECTIVE
OBJECTIVE
To evaluate the efficacy and safety of atezolizumab in BCG-unresponsive high-risk NMIBC.
DESIGN, SETTING, AND PARTICIPANTS
METHODS
This was a single-arm phase 2 trial in patients with BCG-unresponsive high-risk NMIBC who were ineligible for or declined RC.
INTERVENTION
METHODS
Intravenous atezolizumab every 3 wk for 1 yr.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
METHODS
The primary endpoint was the pathological complete response (CR) rate for patients with carcinoma in situ (CIS) determined via mandatory biopsy at 6 mo. Event-free survival (EFS) at 18 mo for patients with non-CIS tumors and treatment-related adverse events (TRAEs) were key secondary endpoints.
RESULTS AND LIMITATIONS
CONCLUSIONS
Of 172 patients enrolled in the trial, 166 received at least one dose of atezolizumab (safety analysis) and 129 were eligible (efficacy analysis). Of the 74 patients with CIS, 20 (27%) experienced a CR at 6 mo. The median duration of response was 17 mo, and 56% (95% confidence interval [CI] 34-77%) of the responses were durable to at least 12 mo. The 18-mo actuarial EFS rate among 55 patients with Ta/T1 disease was 49% (90% CI 38-60%). Twelve of 129 eligible patients experienced progression to muscle-invasive or metastatic disease. Grade 3-5 TRAEs occurred in 26 patients (16%), including three treatment-related deaths. The study was limited by the small sample size and a high rate of patient ineligibility.
CONCLUSIONS
CONCLUSIONS
The efficacy of atezolizumab observed among patients with BCG-unresponsive NMIBC is similar to results from similar trials with other agents, but did not meet the prespecified efficacy threshold. Modest efficacy needs to be balanced with a significant rate of TRAEs and the risk of disease progression when considering systemic immunotherapy in early-stage bladder cancer.
PATIENT SUMMARY
RESULTS
We tested intravenous immunotherapy (atezolizumab) in patients with high-risk non-muscle-invasive bladder cancer that recurred after BCG (bacillus Calmette-Guérin) treatment. Although we found similar outcomes to previous trials, the benefit of this therapy is modest and needs to be carefully balanced with the significant risk of side effects. This trial is registered on ClinicalTrials.gov as NCT02844816.
Identifiants
pubmed: 37596191
pii: S0302-2838(23)03019-1
doi: 10.1016/j.eururo.2023.08.004
pii:
doi:
Substances chimiques
BCG Vaccine
0
atezolizumab
52CMI0WC3Y
Adjuvants, Immunologic
0
Banques de données
ClinicalTrials.gov
['NCT02844816']
Types de publication
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
536-544Subventions
Organisme : NCI NIH HHS
ID : U10 CA180819
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180888
Pays : United States
Informations de copyright
Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.