Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP.
Methods: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP.
Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8–10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82–1.65); failure-free survival HR = 0.51 (95% CI 0.39–0.67); progression-free survival HR = 0.65 (95% CI 0.48–0.88); metastasis-free survival HR = 0.77 (95% CI 0.57–1.03); prostate cancer-specific survival HR = 1.02 (0.70–1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55–1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm.
Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs.
Trial registration
Clinicaltrials.gov: NCT00268476.
Annals of Oncology. 2018 Feb 26 [Epub ahead of print]
M R Sydes,1 M R Spears,1 M D Mason,2 N W Clarke,3 D P Dearnaley,4 J S de Bono,4 G Attard,5 S Chowdhury,6 W Cross,7 S Gillessen,8,9,10 Z I Malik,11 R Jones,12,13 C C Parker,4,14 A W S Ritchie,1 J M Russell,12,13 R Millman,1 D Matheson,15 C Amos,1 C Gilson,1 A Birtle,16 S Brock,17 L Capaldi,18 P Chakraborti,19 A Choudhury,20,21,22 L Evans,23 D Ford,24 J Gale,25 S Gibbs,26 D C Gilbert,27 R Hughes,28 D McLaren,29 J F Lester,30 A Nikapota,31 J O’Sullivan,32,33 O Parikh,34 C Peedell,35 A Protheroe,36 S M Rudman,6 R Shaffer,37 D Sheehan,38 M Simms,39 N Srihari,40 R Strebel,41,42 S Sundar,43 S Tolan,11 D Tsang,44 M Varughese,45 J Wagstaff,46 M K B Parmar,1 N D James,47 and The STAMPEDE Investigators
1. MRC Clinical Trials Unit at UCL, London, United Kingdom
2. Cardiff University, Cardiff, United Kingdom
3. Christie and Royal Salford Hospital, Manchester, United Kingdom
4. Institute of Cancer Research, Sutton, United Kingdom
5. UCL Cancer Institute, University College London, London, United Kingdom
6. Guy's & St Thomas NHS, Foundation Trust, London, United Kingdom
7. St James University Hospital, Leeds, United Kingdom
8. Division of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland
9. University of Bern, Bern, Switzerland
10. Swiss Group for Cancer Clinical Research (SAKK), Bern, Switzerland
11. The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, United Kingdom
12. Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland
13. Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, Scotland
14. Royal Marsden Hospital, Sutton, United Kingdom
15. Faculty of Education, Health and Wellbeing, University of Wolverhampton, Wolverhampton, United Kingdom
16. Rosemere Cancer Centre, Royal Preston Hospital, Preston, United Kingdom
17. Dorset Cancer Centre, Poole Hospital, Poole, Unied Kingdom
18. Worcestershire Acute Hospitals NHS Trust, Worcester, United Kingdom
19. Royal Derby Hospital, Derby, United Kingdom
20. Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
21. Manchester Academic Health Science Centre, Manchester, United Kingdom
22. Christie Hospital NHS Foundation Trust, Manchester, United Kingdom
23. Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
24. City Hospital, Cancer Centre at Queen Elizabeth Hospital, Birmingham, United Kingdom
25. Portsmouth Oncology Centre, Queen Alexandra Hospital, Portsmouth, United Kingdom
26. Queen's Hospital, Romford, United Kingdom
27. Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, United Kingdom
28. Mount Vernon Group, Mount Vernon Hospital, Middlesex, United Kingdom
29. Western General Hospital, Edinburgh, Scotland
30. Velindre Cancer Centre, Cardiff, United Kingdom
31. Sussex Cancer Centre, Brighton, United Kingdom
32. Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, Northern Ireland
33. Belfast City Hospital, Belfast, Northern Ireland
34. Lancashire Teaching Hospitals NHS Trust, Preston, United Kingdom
35. Department of Oncology & Radiotherapy, South Tees NHS Trust, Middlesbrough, United Kingdom
36. Oxford University Hospitals NHS Foundation Trust, United Kingdom
37. Department of Oncology, Royal Surrey County Hospital, Guildford, United Kingdom
38. Royal Devon and Exeter Hospital, Exeter, United Kingdom
39. Hull & East Yorkshire Hospitals NHS Trust, Hull, United Kingdom
40. Shrewsbury and Telford Hospitals NHS Trust, Shrewsbury, United Kingdom
41. Kantonsspital Graubünden, Chur, Switzerland
42. Swiss Group for Cancer Clinical Research (SAKK), Bern, Switzerland
43. Department of Oncology, Nottingham, University Hospitals NHS Trust, Nottingham, United Kingdom
44. Southend Hospital, Southend-on-Sea, Essex, United Kingdom
45. Musgrove Park Hospital, Taunton and Somerset NHS Foundation Trust, Somerset, United Kingdom
46. Swansea University College of Medicine, Swansea, United Kingdom
47. Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom