Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476).
James, Nicholas D Clarke, Noel W Cook, Adrian Ali, Adnan Hoyle, Alex P Attard, Gerhardt Brawley, Christopher D Chowdhury, Simon Cross, William R Dearnaley, David P
James, Nicholas D
Clarke, Noel W
Cook, Adrian
Ali, Adnan
Hoyle, Alex P
Attard, Gerhardt
Brawley, Christopher D
Chowdhury, Simon
Cross, William R
Dearnaley, David P
Citations
Altmetric:
Affiliation
The Institute of Cancer Research; The Christie NHS Foundation Trust; Northern Care Alliance NHS Foundation Trust; Sandwell and West Birmingham NHS Trust; et al.
Other Contributors
Publication date
2022-05-16
Subject
Collections
Research Projects
Organizational Units
Journal Issue
Abstract
Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomised 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 and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years 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 = 0.31 × 10-9 ) favoured SOC + AAP, with 5-years 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 and 8.1 years. Toxicity at 4 years postrandomisation 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.
Citation
James ND, Clarke NW, Cook A, Ali A, Hoyle AP, Attard G, Brawley CD, Chowdhury S, Cross WR, Dearnaley DP, de Bono JS, Diaz-Montana C, Gilbert D, Gillessen S, Gilson C, Jones RJ, Langley RE, Malik ZI, Matheson DJ, Millman R, Parker CC, Pugh C, Rush H, Russell JM, Berthold DR, Buckner ML, Mason MD, Ritchie AWS, Birtle AJ, Brock SJ, Das P, Ford D, Gale J, Grant W, Gray EK, Hoskin P, Khan MM, Manetta C, McPhail NJ, O'Sullivan JM, Parikh O, Perna C, Pezaro CJ, Protheroe AS, Robinson AJ, Rudman SM, Sheehan DJ, Srihari NN, Syndikus I, Tanguay JS, Thomas CW, Vengalil S, Wagstaff J, Wylie JP, Parmar MKB, Sydes MR; STAMPEDE Trials Collaborative Group. Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer. 2022 Aug 1;151(3):422-434. doi: 10.1002/ijc.34018.
Type
Article