Abstract 4951
Background
Despite multiple retrospective studies have demonstrated the clinical validity of molecularly-guided therapy selection in metastatic castrate-resistant prostate cancer (mCRPC), none have validated the actual clinical utility in the context of a randomised controlled trial. We hypothesise that treatment decisions based on plasma-derived cell-free DNA (cfDNA) profiling will increase progression-free survival (primary endpoint), which would result in prolonged overall survival and improved quality-of-life (secondary endpoints).
Trial design
The Prostate Biomarker (ProBio) trial is a recently-initiated adaptive, multi-arm, open-label, multiple assignment randomized controlled biomarker driven phase 3 trial in men with mCRPC. Men (n = 750) will be randomized to receive either standard of care or an experimental treatment with abiraterone acetate, enzalutamide, docetaxel, cabazitaxel, or carboplatin based on molecular biomarker signatures, as inferred from our liquid biopsy profiling. Therefor a prostate-specific1.48 Mb biomarker panel was designed and validated, which is capable of detecting 1) mutations in 78 genes, 2) genomic structural rearrangements in 11 prostate cancer-associated genes, 3) genome-wide copy number alterations, 4) 63 microsatellites to infer microsatellite instability, 4) tumour mutational burden and 5) estimate the circulating tumour DNA (ctDNA) fraction. The initial pre-defined biomarker signatures are defined as tumour properties or mutations in certain genes/pathways identified in the scientific literature as potentially important in prostate cancer treatment response encompassing the androgen receptor (AR), TP53, DNA-repair deficiency (DRD) and the TMPRSS2-ERG fusion. The statistical design of ProBio is novel, since the randomisation probabilities for a given experimental systemic therapy are subjective to change as the trial evolves and learns from prior experience. Secondly, ProBio implements a re-randomization of non-responding patients.
Clinical trial identification
2018-002350-78 (16/07/2018), NCT03903835 (29/03/2019).
Editorial acknowledgement
Legal entity responsible for the study
ProBio Investigators.
Funding
The Swedish Research Council, The Erling-Persson Family Foundation, The Swedish Cancer Foundation.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2036 - Salivary metabolomics for colorectal cancer detection
Presenter: Hiroshi Kuwabara
Session: Poster Display session 3
Resources:
Abstract
1868 - Evaluation and diagnostic potential of plasma biomarkers in bladder cancer
Presenter: Veronika Voronova
Session: Poster Display session 3
Resources:
Abstract
3655 - Liquid biopsy assays using combined circulating tumor cells and circulating tumor DNA in the same patients for the diagnosis of primary lung cancer
Presenter: Yongjoon Suh
Session: Poster Display session 3
Resources:
Abstract
3685 - Peripheral Cytotoxic T Cell Correlates with Tumor Mutational Burden and is Predictive for Progression Free Survival in Advanced Breast Cancer
Presenter: Xiao-ran Liu
Session: Poster Display session 3
Resources:
Abstract
1050 - Splenic Metabolic Activity as Biomarker in Cervical Cancer
Presenter: Emiel De Jaeghere
Session: Poster Display session 3
Resources:
Abstract
1413 - Identification of distinct subtypes revealing prognostic and therapeutic relevance in diffuse type gastric cancer
Presenter: Seon-Kyu Kim
Session: Poster Display session 3
Resources:
Abstract
2140 - Recurrence risk evaluation in stage IB/IIA gastric cancer with TP53 codon 72 polymorphisms
Presenter: Satoshi Nishizuka
Session: Poster Display session 3
Resources:
Abstract
1573 - Identification and validation of a prognostic 4 genes signature for hepatocellular carcinoma: integrated ceRNA network analysis
Presenter: Yongcong Yan
Session: Poster Display session 3
Resources:
Abstract
1196 - Plasma KIM-1 is associated with clinical outcomes after resection for localized renal cell carcinoma: A trial of the ECOG-ACRIN Research Group (E2805)
Presenter: Wenxin Xu
Session: Poster Display session 3
Resources:
Abstract
2657 - Prognostic immunoprofiling of muscle invasive bladder cancer (MIBC) patients in a multicentre setting
Presenter: Katharina Nekolla
Session: Poster Display session 3
Resources:
Abstract