Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
20 Aug 2024
20 Aug 2024
Historique:
received:
13
01
2024
accepted:
19
07
2024
medline:
21
8
2024
pubmed:
21
8
2024
entrez:
20
8
2024
Statut:
aheadofprint
Résumé
ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician's choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB). Secondary endpoints included overall survival and (serious) adverse events. Upon reaching the time to NLCB, patients could be re-randomized. The primary endpoint was met after 218 randomizations. ARPIs demonstrated ~50% longer time to NLCB compared to taxanes (median, 11.1 versus 6.9 months) and the physician's choice arm (median, 11.1 versus 7.4 months) in the biomarker-unselected or 'all' patient population. ARPIs demonstrated longer overall survival (median, 38.7 versus 21.7 and 21.8 months for taxanes and physician's choice, respectively). Biomarker signature findings suggest that the largest increase in time to NLCB was observed in AR (single-nucleotide variant/genomic structural rearrangement)-negative and TP53 wild-type patients and TMPRSS2-ERG fusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53-altered patients. In summary, ARPIs outperform taxanes and physician's choice treatment in patients with metastatic castration-resistant prostate cancer with detectable circulating tumor DNA. ClinicalTrials.gov registration: NCT03903835 .
Identifiants
pubmed: 39164518
doi: 10.1038/s41591-024-03204-2
pii: 10.1038/s41591-024-03204-2
doi:
Banques de données
ClinicalTrials.gov
['NCT03903835']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Vlaamse Liga Tegen Kanker (Flemish Cancer League)
ID : STI.VLK.2020.0006.01
Organisme : Vlaamse Liga Tegen Kanker (Flemish Cancer League)
ID : STI.VLK.2022.0005.01
Organisme : Vlaamse Liga Tegen Kanker (Flemish Cancer League)
ID : STI.VLK.2022.0005.01
Organisme : Krebsliga Beider Basel (Cancer League of Basel-City and Basel-Country)
ID : KLbB-5580-02-2022
Organisme : Cancerfonden (Swedish Cancer Society)
ID : 21 1610 P
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2021-00331
Informations de copyright
© 2024. The Author(s).
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