Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial

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 .

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Publication Details

Journal
Nature Medicine
Published
2024-08-20
DOI
https://doi.org/10.1038/s41591-024-03204-2
Citations
18
Primary Topic
Prostate Cancer Treatment and Research
Type
article
Field-Weighted Citation Impact
7.54

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article

Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial

Sanne D’hondt, Camilla Thellenberg‐Karlsson, Ashkan Mortezavi, Maria Persson et al.
18 citations
Nature Medicine
Prostate Cancer Treatment and Research
7.54
article

Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial

Sanne D’hondt, Camilla Thellenberg‐Karlsson, Ashkan Mortezavi, Maria Persson, Jochen Darras, S. Johansson, Rebecka Bergström, Henrik Grönberg, Jan Vanwelkenhuyzen, Ingrida Verbiené, Johan Sandzén, Michiel Strijbos, Johan Lindberg, Daan De Maeseneer, Christophe Ghysel, Bram De Laere, Peter Schatteman, Markus Mayrhofer, Siska Van Bruwaene, Gunilla Enblad, Venkatesh Chellappa, Martin Eklund, Brieuc Sautois, Maria Nyre Vigmostad, Mats Anden, Daisy Luyten, Piet Ost, Wendy De Roock, Nicolaas Lumen, Elin Jänes, Marie Hjälm-Eriksson, Anders Ullén, Els Everaert, Mahsan Banijamali, Alessio Crippa, Jan Oldenburg, Anastasijia Kotsalaynen, Bjørg Y. Aksnessether, Andrea Discacciati, Martha Olsson, Berit Larsson, Linn Pettersson, Céline Schelstraete
article en
18 citations

Abstract

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 .

Nature MedicineVol. 30(11)
Uppsala University (SE), Karolinska University Hospital (SE), Uppsala University Hospital (SE), University of Zurich (CH), Stavanger University Hospital (NO), Science for Life Laboratory (SE), Akershus University Hospital (NO), AZ Groeninge (BE), Ghent University Hospital (BE), University Hospital of Basel (CH), Karolinska Institutet (SE), Ghent University (BE), Falun Hospital (SE), GZA Ziekenhuizen Campus Sint-Augustinus (BE), Jessa Hospital (BE), Ålesund Hospital (NO), University Hospital of Umeå (SE), Saint Göran Hospital (SE), University Hospital of Zurich (CH), Onze Lieve Vrouwziekenhuis Hospital (BE), AZ Sint-Lucas (BE), Karlstad Central Hospital (SE), AZ Sint-Jan (BE), Länssjukhuset Sundsvall-Härnösand (SE), Vlaamse Vereniging voor Obstetrie en Gynaecolo (BE), Damiaan Dicht bij het leven (BE), Centre Hospitalier Universitaire de Liège (BE), Länssjukhuset i Kalmar (SE), See-Spital (CH), Centrallasarettet Växjö (SE), Stadtspital Waid (CH), Ziekenhuis Oost-Limburg (BE)
Cancerfonden, Karolinska Institutet, Vetenskapsrådet, Vlaamse Liga Tegen Kanker, Krebsliga Beider Basel, Kom op tegen Kanker
Good health and well-being
Openalex Percentile: Top 2%
Prostate Cancer Treatment and Research
7.54
DOIOpen Access PDFOpenAlex
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