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Randomized Controlled Trial
. 2022 Aug 1;151(3):422-434.
doi: 10.1002/ijc.34018. Epub 2022 May 16.

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

Nicholas D James  1 , Noel W Clarke  2 , Adrian Cook  3 , Adnan Ali  4 , Alex P Hoyle  5 , Gerhardt Attard  6 , Christopher D Brawley  3 , Simon Chowdhury  7 , William R Cross  8 , David P Dearnaley  9 , Johann S de Bono  1 , Carlos Diaz-Montana  3 , Duncan Gilbert  3 , Silke Gillessen  10 , Clare Gilson  3   11 , Rob J Jones  12 , Ruth E Langley  3 , Zafar I Malik  13 , David J Matheson  14 , Robin Millman  15 , Chris C Parker  16 , Cheryl Pugh  3 , Hannah Rush  3   17 , J Martin Russell  18   19 , Dominik R Berthold  20 , Michelle L Buckner  3 , Malcolm D Mason  21 , Alastair W S Ritchie  22 , Alison J Birtle  23 , Susannah J Brock  24 , Prantik Das  25 , Dan Ford  26 , Joanna Gale  27 , Warren Grant  28 , Emma K Gray  29 , Peter Hoskin  30 , Mohammad M Khan  31   32 , Caroline Manetta  33 , Neil J McPhail  34 , Joe M O'Sullivan  35 , Omi Parikh  36 , Carla Perna  37 , Carmel J Pezaro  38 , Andrew S Protheroe  39 , Angus J Robinson  40 , Sarah M Rudman  17 , Denise J Sheehan  41 , Narayanan N Srihari  42 , Isabel Syndikus  13 , Jacob S Tanguay  43 , Carys W Thomas  44 , Salil Vengalil  45 , John Wagstaff  46 , James P Wylie  4 , Mahesh K B Parmar  3 , Matthew R Sydes  3 ; STAMPEDE Trials Collaborative Group
Affiliations
Randomized Controlled Trial

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

Nicholas D James et al. Int J Cancer. .

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.

Keywords: abiraterone; clinical trial; hormone therapy; phase III; prostate cancer; randomised controlled trial; survival.

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Conflict of interest statement

Gerhard Attard received personal fees from Sanofi Aventis, Astellas, Medivation, Novartis, Millennium Pharmaceuticals, Abbott Laboratories, Essa Pharmaceuticals, Bayer Healthcare Pharmaceuticals, Takeda, Janssen, Veridex, Roche/Ventana, Pfizer, the Institute of Cancer Research (ICR); grants from Astra Zeneca, Arno therapeutics, Innocrin Pharma, Janssen; and Royalty income from Institute of Cancer Research abiraterone, share of income through ICR's Rewards to discoverers scheme.

Alison J. Birtle served on Advisory Boards for Astellas, Bayer, Janssen, Roche, MSD, Merck, Pfizer, BMS, Astra Zeneca and has speaker fees and travel support from Bayer, Janssen, Sanofi, Astellas. Simon Chowdhury received speaker fees and/or article writing and/or educational events from Astra Zeneca, Novartis/AAA, Clovis Oncology, Janssen, Bayer, Pfizer, Beigene & Astellas; is an advisory board member of Astellas, Janssen, Novartis/AAA, Bayer, Astellas, Athenex, Beigene, Clovis Oncology. He received consulting fees from Telix, Remedy Bio, Huma; research support from Clovis Oncology; and meeting/travel expenses from Janssen, Beigene; he is the founder of Curve. life and earns stock of Curve. life, Huma, Remedy Bio. Noel W Clarke received honoraria from Astellas & Janssen; took a consulting/advisory role for Astellas, Janssen, Ferring, Bayer & Sanofi; was paid speakers fees from Janssen & Astellas; received funding for the institution from Astra Zeneca; received meeting and travel expenses from Janssen, Astellas, Sanofi, Astra Zeneca, Ferring & Ipsen. Prof D. Dearnaley is an advisory board member for Janssen Pharma; holds European patent EP1933709B1 (pending in Canada and India) for a Location and Stabilisation Device; and his previous employer. The Institute of Cancer Research, receives loyalty income from abiraterone from which Prof, Dearnaley receives a share of this income through the ICR's Rewards to Discoverer's Scheme. Johann S. de Bono received personal fees from Amgen, Astellas, Astra Zeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Gentech Roche, Genmab, GlaxoSmithKline, Harpoon, Janssen, Menarini Silicon Biosystems, Merck Serono, Merck Sharpe & Dome, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals; grants received from Astellas, Bayer, Cellcentric, Daiichi, Genmab, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharpe & Dome, Orion Pharma, Pfizer, Sanofi Aventis, Sierra Oncology, Taiho, Vertex Pharmaceuticals. Other payments received from Amgen, Astellas, Astra Zeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Gentech Roche, Genmab, GlaxoSmithKline, Harpoon, Janssen, Menarini Silicon Biosystems, Merck Serono, Merck Sharpe & Dome, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals; in addition, Prof. De Bono has a patent DNA damage repair inhibitors for treatment of cancer (patent no. WO 2005 053662) licenced to Astra Zeneca, and a patent 17‐substituted steroids useful in cancer treatment; patent no. S 5604213) licenced to Janssen. Silke Gillessen is on the advisory board of Menarini Silicon Biosystems, Aranda, Orion, Amgen, Tolero Pharmaceuticals, Astellas, Janssen, Merck Sharpe & Dome, Bayer, Roche, Pfizer, Telix Pharma, Bristol‐Mysers Squibb, AAA International SA, Novartis, Modra Pharmaceuticals and the steering committee of AMGEN; a speaker: Orikata, SAKK, Beijing Family Hospital, ESMO, Swiss Academy of Multidisciplinary Oncology (SAMO); and on the speakers bureau of Janssen; she received travel/meeting expenses from ProteoMedix and for consultancy for S. Grassi Consulting; other payments received from DESO, RSI, Oncoforum. Clare Gilson received research funding to the institution from Janssen, Clovis Oncology, Sanofi, Astellas, Medical Research Council & Cancer Research UK. Dan Ford received speaker fees and/or article writing and/or educational events from BMS, IPSEN, EUSA, Pfizer, ESAI; they received travel expenses from Janssen & IPSEN. Nicholas D James received research funding to the institution from Astellas, Astra Zeneca & Janssen; receipt of honoraria/fees on the advisory board for Astra Zeneca, Clovis Oncology, Janssen, Merck, Novartis & Sanofi; received fees as a speaker for Bayer & Novartis. Ruth E. Langley received an institutional grant from the MRC. Malcolm D. Mason is an advisory board member for Endocyte & Clovis Oncology. Neil J. McPhail received consulting fees from GlaxoSmithKline, Eisai & IPSEN; received meeting attendance expenses from IPSEN and received conference fees from Bayer. Carmel J. Pezaro received honoraria for lectures from AAA, Astra Zeneca, Janssen, they received meeting/travel support from Bayer & IPSEN. Joe M. O'Sullivan received speaker fees from AAA, Astellas, Bayer, Janssen, Novartis, Sanofi and participated as an advisory board member and/or member of the data safety monitoring board for AAA, Astellas, Bayer, Janssen, Novartis & Sanofi. Sarah Rudman has received speakers fees from Janssen. Mahesh K. B. Parmar received research funding to the Unit he directs from Acoria Pvt Ltd, Akagera, Amgen, Aspirin Foundation, Astellas, AstraZeneca, Baxter, Bayer, BMS US, Bri‐Bio, Cepheid, Cipla, Clovis Inc, CSL Behring, Eli‐Lilly, Emergent Biosolutions, Gilead Sciences, GlaxoSmithKline, Grifols, Janssen Products LP, Janssen‐Cilag, Johnson & Johnson, Micronoma, Modus Theraputics, Mylan, Novartis, Pfizer, Sanofi, Serum Institute of India, Shionogi, Synteny Biotechnology, Takeda, Tibotec, Transgene, ViiV Healthcare, Virco and Xenothera. Narayanan N. Srihari received travel/meeting payments from Janssen. Rob J. Jones received research funding to the institution from Bayer, Astellas & Pfizer; received honoraria on the advisory board for Janssen, Astellas, Bayer, Pfizer; received speaker fees from Janssen, Astellas, Bayer & Pfizer. Matthew R. Sydes received research funding to the institution from Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, Sanofi‐Aventis; received speaker fees from Lilly Oncology & Janssen; independent member of data monitoring committees. The other authors do not declare relevant competing interests for this work.

Figures

FIGURE 1
FIGURE 1
CONSORT diagram
FIGURE 2
FIGURE 2
Overall survival by allocated treatment: 2A ‐ Overall survival by allocated treatment; 2B ‐ Failure‐free survival by allocated treatment [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
Overall survival by allocated treatment and metastatic disease risk group: 3A ‐ high‐risk metastatic disease risk group; 3B ‐ low‐risk metastatic disease risk group [Color figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

Comment in

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