A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer.
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:
01 09 2021
01 09 2021
Historique:
received:
18
01
2021
revised:
23
03
2021
accepted:
03
06
2021
pubmed:
11
6
2021
medline:
5
4
2022
entrez:
10
6
2021
Statut:
ppublish
Résumé
Men with metastatic castration-resistant prostate cancer (mCRPC) have limited treatment options after progressing on hormonal therapy and chemotherapy. Here, we evaluate the safety and efficacy of atezolizumab (anti-PD-L1) + radium-223 dichloride (radium-223) in men with mCRPC. This phase Ib study evaluated atezolizumab + radium-223 in men with mCRPC and bone and lymph node and/or visceral metastases that progressed after androgen pathway inhibitor treatment. Following safety assessment of concurrent dosing, 45 men were randomized 1:1:1 to concurrent or one of two staggered dosing schedules with either agent introduced one cycle before the other. This was followed by a safety-efficacy expansion cohort (randomized 1:1:1). The primary endpoints were safety and objective response rate (ORR) by RECIST 1.1. Secondary endpoints included radiographic progression-free survival (rPFS), PSA responses, and overall survival (OS). As of October 4, 2019, 44 of 45 men were evaluable. All 44 had ≥1 all-cause adverse event (AE); 23 (52.3%) had a grade 3/4 AE. Fifteen (34.1%) grade 3/4 and 3 (6.8%) grade 5 AEs were related to atezolizumab; none were related to radium-223. Confirmed ORR was 6.8% [95% confidence interval (CI), 1.4-18.7], median rPFS was 3.0 months (95% CI, 2.8-4.6), median PSA progression was 3.0 months (95% CI, 2.8-3.3), and median OS was 16.3 months (95% CI, 10.9-22.3). This phase Ib study demonstrated that atezolizumab + radium-223, regardless of administration schedule, had greater toxicity than either drug alone, with no clear evidence of additional clinical benefit for patients with mCRPC and bone and lymph node and/or visceral metastases.
Identifiants
pubmed: 34108181
pii: 1078-0432.CCR-21-0063
doi: 10.1158/1078-0432.CCR-21-0063
pmc: PMC8974420
mid: NIHMS1825084
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Immune Checkpoint Inhibitors
0
atezolizumab
52CMI0WC3Y
Radium-223
8BR2SOL3L1
Radium
W90AYD6R3Q
Banques de données
ClinicalTrials.gov
['NCT02814669']
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4746-4756Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
©2021 The Authors; Published by the American Association for Cancer Research.
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