Safety and Clinical Activity of Atezolizumab in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase I Study.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 06 2021
15 06 2021
Historique:
received:
27
05
2020
revised:
15
12
2020
accepted:
05
02
2021
pubmed:
12
2
2021
medline:
8
4
2022
entrez:
11
2
2021
Statut:
ppublish
Résumé
Atezolizumab [anti-programmed death-ligand 1 (anti-PD-L1)] is well tolerated and efficacious in multiple cancers, but has not been previously evaluated in metastatic castration-resistant prostate cancer (mCRPC). This study examined the safety, efficacy, and biomarkers of atezolizumab monotherapy for mCRPC. This phase Ia, open-label, dose-escalation and dose-expansion study (PCD4989g) enrolled patients with mCRPC who had progressed on sipuleucel-T or enzalutamide. Atezolizumab was given intravenously every 3 weeks until confirmed disease progression or loss of clinical benefit. Prespecified endpoints included safety, efficacy, biomarker analyses, and radiographic assessments. All 35 evaluable patients [median age, 68 years (range, 45-83 years)] received atezolizumab after ≥1 prior line of therapy; 62.9% of patients had received ≥3 prior lines. Treatment-related adverse events occurred in 21 patients (60.0%), with no deaths. One patient had a confirmed partial response (PR) per RECIST 1.1, and 1 patient had a PR per immune-related response criteria. The confirmed 50% PSA response rate was 8.6% (3 patients). Median overall survival (OS) was 14.7 months [95% confidence interval (CI): 5.9-not evaluable], with a 1-year OS rate of 52.3% (95% CI: 34-70); 2-year OS was 35.9% (95% CI: 13-59). Median follow-up was 13.0 months (range, 1.2-28.1 months). Biomarker analyses showed that atezolizumab activated immune responses; however, a composite biomarker failed to reveal consistent correlations with efficacy. Atezolizumab was generally well tolerated in patients with mCRPC, with a safety profile consistent with other tumor types. In heavily pretreated patients, atezolizumab monotherapy demonstrated evidence of disease control; however, its limited efficacy suggests a combination approach may be needed.
Identifiants
pubmed: 33568344
pii: 1078-0432.CCR-20-1981
doi: 10.1158/1078-0432.CCR-20-1981
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
atezolizumab
52CMI0WC3Y
Banques de données
ClinicalTrials.gov
['NCT01375842']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3360-3369Informations de copyright
©2021 American Association for Cancer Research.
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