Using the AR-V7 biomarker to determine treatment in metastatic castrate resistant prostate cancer, a feasibility randomised control trial, conclusions from the VARIANT trial

Gravestock, P. et al. (2023) Using the AR-V7 biomarker to determine treatment in metastatic castrate resistant prostate cancer, a feasibility randomised control trial, conclusions from the VARIANT trial. NIHR Open Research, 2, 49. (doi: 10.3310/nihropenres.13284.2) (PMID:37035713) (PMCID:PMC7614403)

Abstract

Background: Prostate cancer is the most commonly diagnosed malignancy in the UK. Castrate resistant prostate cancer (CRPC) can be difficult to manage with response to next generation hormonal treatment variable. AR-V7 is a protein biomarker that can be used to predict response to treatment and potentially better inform management in these patients. Our aim was to establish the feasibility of conducting a definitive randomised controlled trial comparing the clinical utility of AR-V7 biomarker assay in personalising treatments for patients with metastatic CRPC within the United Kingdom (UK) National Health Service (NHS). Due to a number of issues the trial was not completed successfully, we aim to discuss and share lessons learned herein. Methods: We conducted a randomised, open, feasibility trial, which aimed to recruit 70 adult men with metastatic CRPC within three secondary care NHS trusts in the UK to be run over an 18-month period. Participants were randomised to personalised treatment based on AR-V7 status (intervention) or standard care (control). The primary outcome was feasibility, which included: recruitment rate, retention and compliance. Additionally, a baseline prevalence of AR-V7 expression was to be estimated. Results: Fourteen participants were screened and 12 randomised with six into each arm over a nine-month period. Reliability issues with the AR-V7 assay meant prevalence was not estimated. Due to limited recruitment the study did not complete to target. Conclusions: Whilst the trial did not complete to target, we have ascertained that men with advanced cancer are willing to take part in trials utilising biomarker guided treatment. A number of issues were identified that serve as important learning points in future clinical trials. Keywords

• Item Type: Articles
• Additional Information: Version 2; peer review: 2 approved. This work is funded by the National Institute for Health and Care Research (NIHR) Research under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB‐PG‐0816‐20043).
• Keywords: Male, prostatic neoplasms, biomarkers, feasibility studies, castration-resistant.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jones, Professor Robert
• Authors: Gravestock, P., Clark, E., Morton, M., Sharma, S., Fisher, H., Walker, J., Wood, R., Hancock, H., Waugh, N., Cooper, A., Maier, R., Marshall, J., Chandler, R., Bahl, A., Crabb, S., Jain, S., Pedley, I., Jones, R., Staffurth, J., and Heer, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: NIHR Open Research
• Publisher: F1000Research
• ISSN: 2633-4402
• ISSN (Online): 2633-4402
• Published Online: 02 September 2022
• Copyright Holders: Copyright © 2023 Gravestock P et al.
• First Published: First published in NIHR Open Research 2: 49
• Publisher Policy: Reproduced under a Creative Commons License