Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5‐year follow‐up results from the STAMPEDE randomised trial (NCT00268476)

James, N. D. et al. (2022) Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5‐year follow‐up results from the STAMPEDE randomised trial (NCT00268476). International Journal of Cancer, 151(3), pp. 422-434. (doi: 10.1002/ijc.34018) (PMID:35411939)

Abstract

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multi-arm, multi-stage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 yrs after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomized patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards & flexible parametric models, adjusted for baseline stratification factors. 1003 patients were contemporaneously randomized (Nov-2011--Jan-2014): median age 67 yr; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% un-assessable; median PSA 97 ng/mL. At 6.1 yr median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC + AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0·60 (95%CI:0·50—0·71; P = 0.31x10−9) favoured SOC + AAP, with 5-yr survival improved from 41% SOC-alone to 60% SOC + AAP. This was similar in low-risk (HR = 0·55; 95%CI:0·41—0·76) and high-risk (HR = 0·54; 95%CI:0·43—0·69) patients. Median and current maximum time on SOC + AAP was 2.4 yr and 8.1 yr. Toxicity at 4 yr post-randomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.

• Item Type: Articles
• Additional Information: The sponsor was University College London, transferred during the comparison from the UK Medical Research Council (MRC). The trial was conducted by the MRC Clinical Trials Unit at UCL. In the United Kingdom, it was funded by Cancer Research UK (CRUK_A12459) and the Medical Research Council (MRC_MC_UU_12023/25, MC_UU_00004/01), and supported by the UK Clinical Research Network. In Switzerland, it was funded by the Swiss Group for Cancer Clinical Research (SAKK). Industry collaboration and support for this comparison has been provided to the STAMPEDE protocol by Janssen. Further support to STAMPEDE has been provided by Astellas, Clovis Oncology, Janssen, Novartis, Pfizer and Sanofi-Genzyme. NDJ, CCP and DPD were supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jones, Professor Robert and Russell, Dr Martin
• Authors: James, N. D., Clarke, N. W., Cook, A., Ali, A., Hoyle, A. P., Attard, G., Brawley, C. D., Chowdhury, S., Cross, W. R., Dearnaley, D. P., Bono, J. S., Montana, C. D., Gilbert, D., Gillessen, S., Gilson, C., Jones, R. J., Langley, R. E., Malik, Z. I., Matheson, D. J., Millman, R., Parker, C. C., Pugh, C., Rush, H., Russell, J. M., Berthold, D. R., Buckner, M. L., Mason, M. D., Ritchie, A. W.S., Birtle, A. J., Brock, S. J., Das, P., Ford, D., Gale, J., Grant, W., Gray, E. K., Hoskin, P., Khan, M. M., Manetta, C., McPhail, N. J., O'Sullivan, J. M., Parikh, O., Perna, C., Pezaro, C. J., Protheroe, A. S., Robinson, A. J., Rudman, S. M., Sheehan, D. J., Srihari, N. N., Syndikus, I., Tanguay, J., Thomas, C. W., Vengalil, S., Wagstaff, J., Wylie, J. P., Parmar, M. K.B., and Sydes, M. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: International Journal of Cancer
• Publisher: Wiley
• ISSN: 1097-0215
• ISSN (Online): 1097-0215
• Published Online: 12 April 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in International Journal of Cancer 151(3): 422-434
• Publisher Policy: Reproduced under a Creative Commons License