A Repurposing Programme Evaluating Repurposing Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design.

Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer.

The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately.

to date: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited.

Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.

Clinical oncology (Royal College of Radiologists (Great Britain)). 2023 Nov 08 [Epub ahead of print]

D C Gilbert, M Nankivell, H Rush, N W Clarke, S Mangar, A Al-Hasso, S Rosen, R Kockelbergh, S K Sundaram, S Dixit, M Laniado, N McPhail, A Shaheen, S Brown, J Gale, J Deighan, J Marshall, T Duong, A Macnair, A Griffiths, C L Amos, M R Sydes, N D James, M K B Parmar, R E Langley

MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK; University Hospitals Sussex NHS Foundation Trust, Royal Sussex County Hospital, Brighton, UK. Electronic address: ., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK., The Christie and Salford Royal Hospitals, Manchester, UK., Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK., Beatson West of Scotland Cancer Centre, Glasgow, UK., National Heart and Lung Institute, Imperial College, London, UK., Department of Urology, University Hospitals of Leicester, Leicester, UK., Mid-Yorkshire Teaching NHS Trust, Pinderfields Hospital, Wakefield, UK., Scunthorpe General Hospital, Scunthorpe, UK., Wexham Park Hospital, Slough, UK., Raigmore Hospital, Inverness, UK., Singleton Hospital, Swansea, UK., Airedale General Hospital, Keighley, UK., Queen Alexandra Hospital, Portsmouth, UK., Patient Representative, MRC Clinical Trials Unit at UCL, London, UK., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK; Guys and St Thomas' NHS Foundation Trust, London, UK., Institute of Cancer Research, Sutton, UK.