{"id":46768,"date":"2024-09-06T07:00:00","date_gmt":"2024-09-06T07:00:00","guid":{"rendered":"http:\/\/f580a768befd55e655e6e7cedc8ebfad"},"modified":"2024-11-03T15:11:47","modified_gmt":"2024-11-03T15:11:47","slug":"androgen-receptor-pathway-inhibitors-outperform-taxanes-in-patients-with-mcrpc-with-detectable-ctdna","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/androgen-receptor-pathway-inhibitors-outperform-taxanes-in-patients-with-mcrpc-with-detectable-ctdna\/","title":{"rendered":"Androgen Receptor Pathway Inhibitors Outperform Taxanes in Patients with mCRPC with Detectable ctDNA"},"content":{"rendered":"

First results of the Prostate Biomarkers (ProBio) platform study demonstrate that, on average, androgen receptor pathway inhibitors outperform taxanes in all circulating tumour DNA (ctDNA)-positive patients with metastatic castration-resistant prostate cancer (mCRPC) who are androgen receptor pathway inhibitors-naive and with or without prior docetaxel exposure. This may be particularly the case in androgen receptor (AR<\/em>) single-nucleotide variant\/genomic structural rearrangement-negative and TP53<\/em> wild-type tumours or TMPRSS2\u2013ERG <\/em>fusion-positive tumours. Conversely, new treatment strategies might be relevant to patients with TP53<\/em>-altered tumours considering their poor and similar short-term outcomes, irrespective of a treatment with androgen receptor pathway inhibitors or taxanes.<\/p>\n

Furthermore, ProBio\u2019s biomarker-driven and outcome-adaptive design shows the feasibility of using ctDNA for treatment personalisation and may represent a new model for precision medicine trials in oncology. The findings are published by Dr. Henrik Gr\u00f6nberg of the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and Prostatacancer Centrum, Capio S:t G\u00f6rans Sjukhus in Stockholm, Sweden, and colleagues on 20 August 2024 in the Nature Medicine<\/em>.<\/p>\n

mCRPC is a genetically and clinically heterogeneous disease that can be treated with different classes of systemic agents. Retrospective analyses suggest that different tumour genotypes yield varying therapeutic benefits. Although several prognostic biomarkers have been identified, the number of biomarkers predictive of therapeutic and clinical benefit remains small. The authors wrote in the background that one reason for this is that traditional clinical trials have not been biomarker-driven.<\/p>\n

ProBio is the first outcome-adaptive platform trial in prostate cancer utilising a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective ctDNA and germline DNA analysis was performed in patients with mCRPC before randomisation to androgen receptor pathway inhibitors, taxanes, or a physician\u2019s choice control arm. The primary endpoint was the time to no longer clinically benefitting. Secondary endpoints included overall survival (OS) and (serious) adverse events.<\/p>\n

Upon reaching the time to no longer clinically benefitting, patients could be re-randomiaed. The primary endpoint was met after 218 randomisations. Androgen receptor pathway inhibitors demonstrated approximately 50% longer time to no longer clinically benefitting compared to taxanes with median 11.1 versus 6.9 months and the physician\u2019s choice arm with median 11.1 versus 7.4 months in the biomarker-unselected or all patient population.<\/p>\n

Androgen receptor pathway inhibitors demonstrated longer OS with median 38.7 versus 21.7 and 21.8 months for taxanes and physician\u2019s choice, respectively. Biomarker signature findings suggest that the largest increase in time to no longer clinically benefitting was observed in AR <\/em>single-nucleotide variant\/genomic structural rearrangement-negative and TP53 <\/em>wild-type tumours and TMPRSS2\u2013ERG <\/em>fusion-positive tumours, whereas no difference between androgen receptor pathway inhibitors and taxanes was observed in patients with TP53<\/em>-altered tumours.<\/p>\n

ProBio\u2019s platform design, trial infrastructure and real-time liquid biopsy profiling have successfully enabled continuous and prospective evaluation of systemic agents and cell-free DNA biomarkers, providing a new way to identify subsets of patients benefiting differentially from a particular treatment class.<\/p>\n

The authors concluded that study initial results demonstrate the superiority of androgen receptor pathway inhibitors for the biomarker-unselected all patient population compared to physician\u2019s choice and taxanes in patients with mCRPC and detectable ctDNA. They further provided randomised-controlled insights into the treatment-predictive potential of the selected biomarker signatures and proposed novel ctDNA-defined patient subpopulations with differential treatment outcomes.<\/p>\n

The study findings suggest that patients with TMPRSS2\u2013ERG <\/em>fusion-positive tumours may benefit more from androgen receptor pathway inhibitors compared to taxanes. In addition, ProBio provides supporting evidence that the inferior outcomes in TP53<\/em>-altered mCRPC are regardless of whether androgen receptor pathway inhibitors or taxanes were administered. This emphasizes the need for alternative treatment strategies and echoes the previously made recommendation for careful monitoring of patients with TP53<\/em>-altered tumours who are more likely to rapidly progress. OS data indicate that these patients may still benefit from androgen receptor pathway inhibitor, although to a lesser extent compared to patients harbouring other biomarker signatures.<\/p>\n

The authors acknowledged the biobanks of the Karolinska Institutet and HIRUZ in Ghent, Belgium for weekly processing of the biomaterial for genomic analysis. They also acknowledged the Clinical Genomics in Stockholm, Sweden and National Bioinformatics Infrastructure Sweden in Uppsala, Sweden for providing timely and cost-efficient DNA sequencing and analysis services. Following funding organisations awarded research grants: ALF Medicine, Swedish Cancer Society, Swedish Research Council, Krebsliga beider Basel and Kom Op Tegen Kanker\/Stand up to Cancer \u2013 Flemish Cancer Society.<\/p>\n

Reference<\/h3>\n

De Laere B, Crippa A, Discacciati A, et al.<\/em> Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial<\/a>. Nature Medicine<\/em>; Published online 20 August 2024. DOI: https:\/\/doi.org\/10.1038\/s41591-024-03204-2<\/a><\/p>\n

Source<\/a><\/p>","protected":false},"excerpt":{"rendered":"

First results of the Prostate Biomarkers (ProBio) platform study demonstrate that, on average, androgen receptor pathway inhibitors outperform taxanes in all circulating tumour DNA (ctDNA)-positive patients with metastatic castration-resistant prostate cancer (mCRPC) who are androgen receptor pathway inhibitors-naive and with or without prior docetaxel exposure. This may be particularly the case in androgen receptor (AR) […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-46768","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46768","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=46768"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46768\/revisions"}],"predecessor-version":[{"id":46920,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46768\/revisions\/46920"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=46768"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=46768"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=46768"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}