A Phase 1b/2 Study of Atezolizumab with or Without Bacille Calmette-Guérin in Patients with High-risk Non-muscle-invasive Bladder Cancer.
Eur Urol Oncol
; 6(3): 313-320, 2023 06.
Article
em En
| MEDLINE
| ID: mdl-36803840
ABSTRACT
BACKGROUND:
Bacille Calmette-Guérin (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, ANDPARTICIPANTS:
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 STATISTICALANALYSIS:
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 ANDLIMITATIONS:
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. PATIENTSUMMARY:
We studied atezolizumab with and without bacille Calmette-Guérin (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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
/
Neoplasias não Músculo Invasivas da Bexiga
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article