Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial
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Published:2024-08-20
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ISSN:1078-8956
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Container-title:Nature Medicine
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language:en
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Short-container-title:Nat Med
Author:
De Laere BramORCID, Crippa AlessioORCID, Discacciati Andrea, Larsson Berit, Persson Maria, Johansson Susanne, D’hondt SanneORCID, Bergström RebeckaORCID, Chellappa Venkatesh, Mayrhofer Markus, Banijamali Mahsan, Kotsalaynen Anastasijia, Schelstraete Céline, Vanwelkenhuyzen Jan PieterORCID, Hjälm-Eriksson Marie, Pettersson Linn, Ullén Anders, Lumen Nicolaas, Enblad GunillaORCID, Thellenberg Karlsson CamillaORCID, Jänes Elin, Sandzén JohanORCID, Schatteman Peter, Nyre Vigmostad MariaORCID, Olsson Martha, Ghysel Christophe, Sautois BrieucORCID, De Roock Wendy, Van Bruwaene Siska, Anden Mats, Verbiene Ingrida, De Maeseneer DaanORCID, Everaert Els, Darras Jochen, Aksnessether Bjørg Y., Luyten Daisy, Strijbos Michiel, Mortezavi Ashkan, Oldenburg Jan, Ost Piet, Eklund MartinORCID, Grönberg HenrikORCID, Lindberg Johan
Abstract
AbstractProBio 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.
Funder
Vlaamse Liga Tegen Kanker Krebsliga Beider Basel Cancerfonden Vetenskapsrådet
Publisher
Springer Science and Business Media LLC
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