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New Combination of Old Drugs Improves Survival in Patients with Prostate Cancer [ESMO Congress 2021 Press Release]

19 Sep 2021

LUGANO, Switzerland - A novel combination of well-known drugs prolongs survival in patients with hormone/castration-sensitive prostate cancer, according to late breaking research presented at the ESMO Congress 2021. (1,2) The PEACE-1 and STAMPEDE studies found that the addition of abiraterone acetate plus prednisolone (AAP) to standard therapy lengthened survival compared to standard therapy alone.

Commenting on the findings, Dr. Maria De Santis, Chair of Interdisciplinary Urological Oncology, Department of Urology, Charité Universitätsmedizin, Berlin, Germany said: “The findings have the potential to be implemented in our daily practice right away as we do not have to wait for the approval of a new drug. The clearly positive results are reassuring and should convince patients and physicians to intensify the treatment of patients with metastatic and high-risk locally advanced hormone/castration-sensitive prostate cancer early on. I expect this kind of treatment intensification to be implemented as a standard of care.”

For men with metastatic prostate cancer, androgen deprivation therapy (ADT) was the standard of care for decades. In 2015, docetaxel (a chemotherapy agent) was shown to improve survival when added to ADT and in 2017, abiraterone (a next generation hormonal agent) was also shown to improve survival when added to ADT. Until now, though, it was unknown whether one or both agents should be added to ADT to achieve the best outcomes. PEACE-1 found that using three drugs upfront is better than just two in men with metastatic prostate cancer, not only to postpone cancer progression, but also to prolong life. When AAP was added to ADT and docetaxel, men experienced an additional 25% reduction in the risk of death compared to ADT and docetaxel alone.

fizazi-karim

Study author Prof. Karim Fizazi, Medical Oncologist, Institute Gustave Roussy and Professor in Oncology, University of Paris-Saclay, Villejuif, France said: “PEACE-1 is the first trial to establish that triplet treatment should be offered to these men, especially those with the most aggressive cancers (those with multiple metastases). Moreover, additional side-effects with the triplet combination were mostly mild, with very few severe side-effects.”

Fizazi pointed out that for men with high-burden metastatic prostate cancer, the triplet treatment used in PEACE-1 provided 2.5 additional years without cancer progression and approximately 18 additional months of life. “For the first time these men can expect to live more than five years whereas before 2015 their median survival was less than three years. By 2022 all three treatments will be generic drugs which should improve access for patients worldwide.”

Fizazi noted that more follow-up is required in men with low-burden metastatic prostate cancer to accurately assess survival. “Triplet systemic treatment clearly postponed cancer progression in these patients but we need more time to determine whether it improves survival. This also applies to the role of local radiotherapy directed to the primary prostate cancer where we need longer follow-up to establish whether and how to best combine it with systemic treatments.”

STAMPEDE focused on non-metastatic (no spread visible on conventional scans) but high-risk (of spread) prostate cancer. Approximately 20% of localised prostate cancers are high-risk at diagnosis but account for the majority of relapses and consequently deaths in this population. Androgen deprivation is given for two or three years and combining it with local radiotherapy to the prostate and pelvis improves life expectancy. Adding treatments such as docetaxel chemotherapy has been tested and shown to prolong time to relapse but did not prolong life expectancy.

The trial found that at six years, men who had received standard treatment plus AAP for two years had an improvement in metastasis-free survival from 69% to 82%, an improvement in overall survival from 77% to 86% and an improvement in prostate cancer specific survival from 85% to 93% – compared to standard treatment alone.

attard-gerhardt

Study author Prof. Gerhardt Attard, John Black Charitable Foundation Endowed Chair in Urological Cancer Research at University College London, UK said: “Based on these results, all men with high-risk non-metastatic prostate cancer should be considered for two years of abiraterone. This will involve more hospital visits during this period to manage administration of the drug but by reducing subsequent relapse, may reduce the overall burden for both patients and health services.”

Attard noted that more information is needed on the optimal length of AAP therapy. “We did not study different durations of treatment so administering AAP for a shorter time may be equivalent and longer may be even more effective.”

Comparing these results with the current treatment options, De Santis said: “The survival benefit in PEACE-1 is a clear improvement and adds to the advances recently made for patients with metastatic hormone/castration sensitive prostate cancer. With regards to the non-metastatic patients in STAMPEDE, this is a completely new patient group that has not been included in other published trials. The addition of systemic treatment with AAP for at least two years in this population will change our former treatment strategy which has been only ADT plus or minus radiotherapy to the prostate for many years.”

Notes to Editors

Please make sure to use the official name of the meeting in your reports: ESMO Congress 2021

Official Congress Hashtag:  #ESMO21

Disclaimer

This press release contains information provided by the authors of the highlighted abstracts and reflects the content of these abstracts. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.

References

  1. LBA4_PR ‘Abiraterone acetate plus prednisolone (AAP) with or without enzalutamide (ENZ) added to androgen deprivation therapy (ADT) compared to ADT alone for men with high-risk non-metastatic (M0) prostate cancer (PCa): Combined analysis from two comparisons in the STAMPEDE platform protocol‘ will be presented by Gerhardt Attard during Presidential Symposium 2 on Sunday, 19 September, 15:05 to 16:37 (CEST) on Channel 1. Annals of Oncology, Volume 32, 2021 Supplement 5
  2. LBA5_PR ‘A phase 3 trial with a 2x2 factorial design in men with de novo metastatic castration-sensitive prostate cancer: overall survival with abiraterone acetate plus prednisone in PEACE-1‘ will be presented by Karim Fizazi during Presidential Symposium 2 on Sunday, 19 September, 15:05 to 16:37 (CEST) on Channel 1. Annals of Oncology, Volume 32, 2021 Supplement 5

G. Attard1, L.C. Brown2, N. Clarke3, L. Murphy2, W. Cross4, R. Jones5, S. Gillessen6, J.M. Russell7, A. Cook8, J. Bowen9, A. Lydon10, I.D. Pedley11, O. Parikh12, S. Chowdhury13, Z. Malik14, D. Matheson15, C. Parker16, M.R. Sydes17, M.K. Parmar18, N.D. James19

1Research Department of Oncology, University College London Cancer Institute, London, UK, 2MRC Clinical Trials Unit, University College London, London, UK, 3Surgery, Manchester University, Manchester, UK, 4Department of Urology, St James University Hospital, Leeds, UK, 5Institute of cancer sciences, BWSCC - Beatson West of Scotland Cancer Centre - NHS Greater Glasgow and Clyde, Glasgow, UK, 6Medical Oncology Department, EOC - Ospedale Regionale Bellinzona e Valli - Istituto Oncologico della Svizzera Italiana (IOSI), Bellinzona, Switzerland, 7Institute of Cancer Sciences, University of Glasgow, Glasgow, UK, 8Clinical Trials Unit, Institute of Clinical Trials and Methodology-UCL, London, UK, 9Oncology, Gloucester NHS Foundation Trust, Gl El, UK, 10Oncology, Torbay and South Devon NHS Foundation Trust, Tqaa, UK, 11Oncology, The Freeman Hospital (NHS Foundation Trust) Northern Centre for Cancer Care, Newcastle-upon-Tyne, Tyne and Wear, UK, 12Oncology, Royal Preston Hospital-Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK, 13Medical Oncology Dept., Guy's and St. Thomas' Hospital NHS Trust, London, UK, 14Oncology, The Clatterbridge Cancer Centre NHS Foundation Trust, L Ya, UK, 15Faculty of Education, Health and Wellbeing, University of Wolverhampton, Wv Ly, UK, 16Department of Urology, The Royal Marsden Hospital NHS Foundation Trust, Sutton, UK, 17MRC Clinical Trials Unit at UCL, Medical Research Council Clinical Trials Unit, London, UK, UK, 18MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology-UCL, London, UK, 19Prostate and Bladder Cancer Research Department, ICR - Institute of Cancer Research, London, UK

Background: Patients (pts) with high-risk M0 PCa are treated with ADT and when indicated, local radiotherapy (RT). Intensifying hormone treatment with AAP, ENZ or apalutamide continuous to progression improves outcomes of metastatic PCa but its efficacy in M0 PCa starting ADT is unknown.

Methods: STAMPEDE is a multi-arm, multi-stage trial that, as part of 2 separate comparisons randomised PCa pts with M0 node positive or high-risk node negative (>1 T3/4, PSA ≥40ng/ml, Gleason 8-10 or relapsing) 1:1 to ADT (control) vs ADT with AAP (1000mg AA + 5mg P od) or ADT vs ADT with AAP + ENZ (160mg od) for 2 years (y), unless RT was omitted when treatment could be to progression. The primary end-point was metastasis-free survival (MFS, time to death or distant metastases). The sub-group of pts who received ADT +/- AAP was partially reported with metastatic pts in 2017 so one-sided type 1 error rate was set to 1.25%. All analyses were pre-specified, pooled using meta-analyses methods and stratified as described previously. Data frozen 3rd August 2021.

Results: 1974 M0 pts at 113 sites in UK & Switzerland were randomised, 914 (Nov 2011 to Jan 2014) to ADT +/- AAP & 1060 (Mar 2016 to Jul 2014) to ADT +/- AAP + ENZ. Groups were well balanced: median age 68 y, range 43-86; median PSA 34 ng/ml, range 0.4-2773; Gleason 8-10, 79%; node positive 39%; planned for RT 85%. Median months to stopping AAP, 23.7 (IQR: 17.6-24.1); AAP when given with ENZ, 20.7 (IQR: 4.4-24); ENZ, 23.2 (IQR: 6.3-24). 180 MFS events occurred in the research group and 306 in the control group. AAP-based therapy improved MFS (HR 0.53, 95% CI 0.44-0.64, P=2.9×10- 11) & survival (HR 0.60, 95% CI 0.48-0.73, P=9.3×10-7): 6-y MFS from 69% to 82%, 6-y survival from 77% to 86%. Treatment effect was consistent in major subgroups and between AAP & AAP + ENZ randomisation periods (MFS HR=0.54, 95% CI 0.43-0.68; HR=0.53, 95% CI 0.39-0.71 respectively; interaction HR = 1.02, 95% CI: 0.70-1.50, p=0.908).

Conclusions: 2 y of AAP-based therapy significantly improves MFS & survival of high-risk M0 PCa starting ADT and should be considered a new standard of care.

Clinical trial identification: NCT00268476.

Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London.

Funding: Cancer Research UK, Medical Research Council, Astellas, Janssen.

Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker, null: Janssen; Financial Interests, Personal, Advisory Board, null: Janssen; Financial Interests, Personal, Invited Speaker, null: Astellas; Financial Interests, Personal, Advisory Board, null: Astellas; Financial Interests, Personal, Advisory Board, null: Novartis; Financial Interests, Personal, Advisory Board, null: Bayer; Financial Interests, Personal, Invited Speaker, null: AstraZeneca; Financial Interests, Personal, Advisory Board, null: AstraZeneca; Financial Interests, Personal, Advisory Board, null: Pfizer; Financial Interests, Personal, Advisory Board, null: Sanofi; Financial Interests, Personal, Advisory Board, null: Sapience; Financial Interests, Personal, Advisory Board, null: Orion; Financial Interests, Personal, Royalties, null: Janssen; Financial Interests, Institutional, Research Grant, null: Janssen; Financial Interests, Institutional, Research Grant, null: Astellas; Non-Financial Interests, , Principal Investigator, null: Janssen; Non-Financial Interests, , Advisory Role, null: Janssen; Non-Financial Interests, , Advisory Role, null: AstraZeneca; Non-Financial Interests, , Principal Investigator, null: Astellas.
L.C. Brown: Financial Interests, Institutional, Research Grant, FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca.
N. Clarke: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: AstraZeneca ; Financial Interests, Personal, Invited Speaker: Ferring; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca ; Financial Interests, Personal, Advisory Board: Ferring; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Research Grant: AstraZeneca .
W. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics; Financial Interests, Personal, Invited Speaker, Speaker fee: Janssen; Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer; Financial Interests, Personal, Invited Speaker, Speaker fee: Astellas; Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics.
R. Jones: Financial Interests, Personal, Advisory Board, advisory board attendance: AstraZeneca; Financial Interests, Personal, Advisory Board, advisory board attendance: Astellas; Financial Interests, Personal, Invited Speaker, Honoraria for speaking: Astellas; Financial Interests, Personal, Advisory Board, null: Bayer; Financial Interests, Personal, Invited Speaker, null: Bayer; Financial Interests, Personal, Advisory Board, null: Clovis; Financial Interests, Personal, Advisory Board, null: Exelixis; Financial Interests, Personal, Advisory Board, null: Ipsen; Financial Interests, Personal, Invited Speaker, null: Ipsen; Financial Interests, Personal, Advisory Board, null: Bristol Myers Squipp; Financial Interests, Personal, Invited Speaker, null: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, null: Merck Serono; Financial Interests, Personal, Invited Speaker, null: Merck Serono; Financial Interests, Personal, Advisory Board, null: Merck Sharpe Dome; Financial Interests, Personal, Invited Speaker, null: Merck Sharpe Dome; Financial Interests, Personal, Invited Speaker, null: Pfizer; Financial Interests, Personal, Advisory Board, null: Roche; Financial Interests, Institutional, Other, IDMC membership: Roche; Financial Interests, Personal, Invited Speaker, null: Roche; Financial Interests, Personal, Advisory Board, null: Janssen; Financial Interests, Personal, Invited Speaker, null: Janssen; Financial Interests, Institutional, Other, IDMC member: Stab; Financial Interests, Personal, Advisory Board, null: Novartis / AAA; Financial Interests, Institutional, Invited Speaker, null: Janssen; Financial Interests, Institutional, Invited Speaker, null: Pfizer; Financial Interests, Institutional, Invited Speaker, null: Tail; Financial Interests, Institutional, Invited Speaker, null: AstraZeneca; Financial Interests, Institutional, Invited Speaker, null: BioXcel; Financial Interests, Institutional, Invited Speaker, null: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker, null: Novartis / AAA; Financial Interests, Institutional, Invited Speaker, null: Roche; Financial Interests, Institutional, Invited Speaker, null: MSK.
S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi; Financial Interests, Personal, Advisory Board, 2018, 2019: Orion; Financial Interests, Personal, Advisory Board, 2018: Roche; Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag; Financial Interests, Personal, Advisory Board, 2020: Amgen; Financial Interests, Personal, Invited Speaker, 2020: ESMO; Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX; Financial Interests, Institutional, Advisory Board, 2018, 2019: Bayer; Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag; Financial Interests, Institutional, Advisory Board, 2020: Roche; Financial Interests, Institutional, Advisory Board, 2018: AAA International; Financial Interests, Institutional, Advisory Board, 2018: Menarini Silicon Biosystems; Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma; Financial Interests, Institutional, Advisory Board, 2019: Tolero Pharmaceuticals; Financial Interests, Institutional, Advisory Board, 2020: MSD Merck Sharp & Dohme; Financial Interests, Institutional, Advisory Board, 2020: Pfizer; Financial Interests, Personal, Invited Speaker, 2021: SAKK; Financial Interests, Institutional, Advisory Board, 2021: Telixpharma; Financial Interests, Institutional, Other, Steering Committee 2021: Amgen; Financial Interests, Institutional, Invited Speaker, 2021: DESO; Financial Interests, Institutional, Advisory Board, 2021: BMS; Financial Interests, Institutional, Advisory Board, 2021: AAA International; Financial Interests, Institutional, Advisory Board, 2021: Orion; Financial Interests, Personal, Invited Speaker, 2021: SAKK; Financial Interests, Personal, Invited Speaker, 2021: SAKK; Financial Interests, Institutional, Advisory Board, 2021: Bayer; Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome; Financial Interests, Personal, Other, 2021: RSI (Televisione Svizzera Italiana); Financial Interests, Personal, Invited Speaker, 2021: SAMO - IBCSG; Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas; Non-Financial Interests, , Advisory Role, 2019: Menarini Silicon Biosystems; Non-Financial Interests, , Advisory Role, 2019: Aranda; Non-Financial Interests, , Advisory Role, Continuing: ProteoMediX.
S. Chowdhury: Financial Interests, Personal, Advisory Board, null: Astellas; Financial Interests, Personal, Advisory Board, null: Janssen; Financial Interests, Personal, Invited Speaker, null: Janssen; Financial Interests, Personal, Advisory Board, null: Huma; Financial Interests, Personal, Invited Speaker, null: AstraZeneca ; Financial Interests, Personal, Advisory Board, null: Bayer; Financial Interests, Personal, Invited Speaker, null: Bayer; Financial Interests, Personal, Advisory Board, null: Novartis/AAA; Financial Interests, Personal, Advisory Board, null: Beigene; Financial Interests, Personal, Advisory Board, null: Remedy Bio; Financial Interests, Personal, Advisory Board, null: Athenex; Financial Interests, Personal, Advisory Board, null: Telix; Financial Interests, Personal, Advisory Board, null: Clovis Oncology; Financial Interests, Personal, Stocks/Shares, null: Curve Life; Financial Interests, Institutional, Research Grant, null: Clovis Oncology; Non-Financial Interests, , Advisory Role, Non-compensated advice: NHS England; Non-Financial Interests, , Advisory Role, null: NICE NHS England.
Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer: sanofi; Other, , Other, support to attend meetings or advisory boards in the past: Astellas,Jaansen,Bayer.
C. Parker: Financial Interests, Personal, Advisory Board, Education Steering Committee: Bayer; Financial Interests, Personal, Invited Speaker, Speaker at prostate cancer educational events: Janssen; Financial Interests, Personal, Advisory Board, Advisory board on apalutamide: Janssen; Financial Interests, Personal, Advisory Board, Advisory board: Clarity Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory board on relugolix: Myovant; Financial Interests, Personal, Advisory Board, Advisory board: ITM Oncologics.
M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen; Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly; Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas; Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology; Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Janssen; Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Novartis; Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Pfizer; Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Sanofi.
M.K. Parmar: Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis.
N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca; Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen; Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen; Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi; Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi; Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Clovis; Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Novartis; Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck; Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen; Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Astellas; Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca.
All other authors have declared no conflicts of interest.

K. Fizazi1, J. Carles Galceran2, S. Foulon1, G. Roubaud3, R. McDermott4, A. Fléchon5, B. Tombal6, S. Supiot7, D.R. Berthold8, P. Ronchin9, G. Kacso10, G. Gravis Mescam11, F. Calabro'12, J.F. Berdah13, A. Hasbini14, M. Silva15, A. Thiery-Vuillemin16, I. Latorzeff17, I. Rieger18, A. Bossi19

1Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France, 2Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain, 3Medical Oncology, Institute Bergonié, Bordeaux, France, 4Oncology (Medical Oncology), St Vincent's University Hospital and Cancer Trials Ireland, Dublin, Ireland, 5Department of Medical Oncology, Centre Léon Bérard, Rhones-Alpes, France, 6Urology, Cliniques Universitaires St. Luc - Université Catholique de Louvain, Brussels, Belgium, 7Radiotherapy, ICO Institut de Cancerologie de l'Ouest René Gauducheau, Saint-Herblain, France, 8Medical Oncology Department, CHUV - Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 9Radiotherapy, Centre Azuréen de Cancérologie, Mougins, France, 10Medical Oncology, Amethyst Radiotherapy Center, Bucharest, Romania, 11Medical Oncology Dept., IPC - Institut Paoli-Calmettes, Marseille, France, 12Medical Oncology, Azienda Ospedaliera S. Camillo Forlanini, Rome, Italy, 13Medical Oncology, Clinique Sainte-Marguerite, Hyères, France, 14Medical Oncology, Clinique Pasteur Lanroze, Brest, France, 15Radiotherapy, Centre François Baclesse, Caen, France, 16Medical Oncology, Centre Hospitalier Universitaire de Besançon, Besançon, France, 17Radiation Oncology, Clinique Pasteur, Toulouse, France, 18Clinical Research, Unicancer, Kremlin-Bicêtre, France, 19Radiation Oncology, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France

Background: Since 2015, combining androgen deprivation therapy (ADT) with either docetaxel, androgen signaling inhibitors (ASI), or radiotherapy to the primary tumor (RXT) (for low metastatic burden) was shown to improve overall survival (OS) and has thus become the new standard of care (SOC) in men with mCSPC. It is unknown whether combining those treatments on top of ADT could further increment outcomes. PEACE-1 is a phase 3 trial with a 2x2 factorial design of abiraterone acetate plus prednisone (abiraterone) and/or local radiotherapy. First results show that adding abiraterone to ADT+docetaxel significantly improves rPFS in men with mCSPC (HR: 0.50 (0.40-0.62), p<0.0001) (Fizazi, ASCO 2021).

Methods: 1173 men (57% high-, 43% low-volume) with de novo mCSPC were randomized to SOC, SOC+abiraterone, SOC+RXT or SOC+abiraterone+RXT (SOC was ADT+docetaxel for 710 pts). The overall type I error testing the abiraterone effect was 5% (4.9% for OS, 0.1% for rPFS). In the ADT+docetaxel population, 249 events were required to detect an HR of 0.70 for OS with 80% power.

Results: The median follow-up is 4.4 yrs (n=273 death events in the ADT+docetaxel population). The effect of abiraterone on OS did not interact with the one of RXT (p=0.82) allowing to pool the abiraterone arms together for comparison. OS was improved by abiraterone both in the overall population (HR: 0.83, 95% CI: 0.69-0.99, p=0.034; medians: 5.7 vs 4.7 yrs) and in the ADT+docetaxel population (HR: 0.75, 95% CI: 0.59-0.96, p=0.021; medians: NR vs 4.4 yrs). Among the ADT+docetaxel pts who developed CRPC, 231/263 (88%) then received at least one life-prolonging therapy and 222/263 (84%) at least one ASI in the control arm, compared to 110/141 (78%) and 67/141 (48%) in the abiraterone arm, respectively. Grade 3-5 adverse events reported in >5% of pts in the ADT+docetaxel population included neutropenic fever (5% vs 5%), neutropenia (10% vs 9%), liver toxicity (6% vs 1%) and hypertension (21% vs 13%) in the abiraterone and control arms, respectively.

Conclusions: Adding abiraterone to ADT plus docetaxel improves both rPFS and OS in mCSPC men, even when 84% of mCRPC men from the control arm receive an ASI.

Clinical trial identification: NCT01957436.

Editorial acknowledgement: We thank Sébastien Marion from Unicancer for editing the English.

Legal entity responsible for the study: Unicancer

Funding: Janssen Pharmaceutical NV, Ipsen, Sanofi, PHRC

Disclosure: K. Fizazi: Financial Interests, Institutional, Advisory Board, null: Astellas; Financial Interests, Institutional, Invited Speaker, null: Astellas; Financial Interests, Institutional, Advisory Board, null: Bayer; Financial Interests, Institutional, Invited Speaker, null: Bayer; Financial Interests, Personal, Advisory Board, null: Curevac; Financial Interests, Institutional, Advisory Board, null: Janssen; Financial Interests, Institutional, Invited Speaker, null: Janssen; Financial Interests, Personal, Advisory Board, null: Orion; Financial Interests, Institutional, Invited Speaker, null: Sanofi; Financial Interests, Institutional, Advisory Board, null: AAA; Financial Interests, Institutional, Advisory Board, null: MSD; Financial Interests, Institutional, Invited Speaker, null: MSD; Financial Interests, Institutional, Advisory Board, null: AstraZeneca; Financial Interests, Institutional, Invited Speaker, null: AstraZeneca; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer; Financial Interests, Institutional, Research Grant, Trial chair: Bayer; Financial Interests, Institutional, Research Grant, Trial chair: AstraZeneca; Financial Interests, Institutional, Research Grant, Trial chair: Orion; Financial Interests, Institutional, Research Grant, Trial chair: MSD; Financial Interests, Institutional, Research Grant, Trial chair: BMS; Financial Interests, Institutional, Research Grant, Trial chair: Janssen.
J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Astrazeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Janssen.
G. Roubaud: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Astrazeneca; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Pfizer.
R. McDermott: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Clovis; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Regeneron.
A. Fléchon: Financial Interests, Personal, Expert Testimony: AAA; Financial Interests, Personal, Expert Testimony: Astrazeneca; Financial Interests, Personal, Expert Testimony: Astellas; Financial Interests, Personal, Expert Testimony: Bayer; Financial Interests, Personal, Expert Testimony: Janssen; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Expert Testimony: Sanofi.
B. Tombal: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Ferring; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Myovant; Financial Interests, Personal, Advisory Board: Sanofi.
S. Supiot: Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Bouchara; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Institutional, Principal Investigator: Astrazeneca; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Janssen.
D.R. Berthold: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche.
G. Kacso: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Astrazeneca; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Astrazeneca; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: MSD.
G. Gravis Mescam: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Sanofi.
F. Calabro': Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Astrazeneca; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Pfizer.
A. Thiery-Vuillemin: Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Astrazeneca; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Astellas.
I. Latorzeff: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Janssen.
A. Bossi: Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Bard; Financial Interests, Personal, Advisory Role: Elekta; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Ferring; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Invited Speaker: Janssen.
All other authors have declared no conflicts of interest.

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