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

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

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3