ESMO 2017 Press Release: Patients with High Risk Prostate Cancer May Benefit “Equally” From Two New Treatments

LUGANO-MADRID – Patients with high risk prostate cancer starting long-term hormone therapy may benefit from two new treatments, according to late-breaking results from the STAMPEDE trial presented at the ESMO 2017 Congress in Madrid. (1)

Long-term hormone therapy alone has been the standard of care for patients with high risk locally advanced or metastatic prostate cancer since the 1940s.

STAMPEDE is a platform protocol using a multi-arm, multi-stage design to efficiently investigate a number of new treatments versus standard of care in patients with high risk prostate cancer. It included men who were starting long-term hormonal therapy for the first time. The trial previously found that docetaxel improved survival compared to standard of care (hazard ratio [HR], 0.78), (2) and that abiraterone acetate with prednisolone also improved survival compared to the same standard of care (HR, 0.63). (3)

First author Matthew Sydes, statistician, MRC Clinical Trials Unit, University College London, UK, said: “Right now, oncologists and urologists want to know which combination is preferable, which is why we conducted this analysis.”

The analysis presented today uses prospectively collected data from the STAMPEDE trial to directly compare patients randomised to the docetaxel and abiraterone acetate plus prednisolone (AAP) research arms while both arms of the trial were recruiting. The randomisations overlapped between November 2011 and March 2013. This comparison included 566 patients, of whom 189 were randomised to receive docetaxel and 377 were randomised to receive AAP, both on top of standard of care androgen-deprivation therapy (with radiotherapy for some patients).

The estimate for the primary outcome of overall survival was a HR of 1.16, and the difference between the two treatments was not statistically significant, with confidence intervals capturing estimates favouring both AAP and docetaxel. (4)

For the early outcome measures of failure-free survival and progression-free survival, estimates of treatment effect clearly favoured AAP with HRs of 0.51 and 0.65, respectively. The estimates of treatment effect for late outcome measures of freedom from metastatic progression and freedom from symptomatic skeletal events favoured AAP but the differences between treatment groups were not statistically significant.

Sydes said: “This comparison was of course underpowered, but it is the only data we have to directly compare docetaxel and abiraterone in this setting.”

Professor Nicholas D. James, Chief Investigator of STAMPEDE and Consultant Oncologist at University of Birmingham and Queen Elizabeth Hospital, Birmingham, UK, said: “The individual trials suggested that abiraterone may have a larger effect on survival than docetaxel, but this did not translate into a clear advantage in this study. Both drugs provide a survival advantage over standard of care alone in men with high risk prostate cancer beginning long-term hormone therapy. This study suggests that starting with either drug is acceptable and choice may depend on availability.”

Sydes said: “We could only make this head-to-head comparison because of the platform nature of this protocol.”

Commenting for ESMO, professor Cora N.Sternberg, Chief, Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy, said: “The STAMPEDE trial has a unique design and has prospectively studied more than 9,000 patients with high risk or metastatic hormone sensitive prostate cancer compared to the standard of care. By 2025 it will have reported the results of ten randomised clinical trials.”

“This comparison offers strong evidence for the combination of standard of care plus AAP versus standard of care alone in terms of failure-free survival and progression-free survival and less strong evidence in terms of metastases-free survival and skeletal related events,” she continued. “There was no difference in survival with standard of care plus docetaxel, as compared to standard of care plus AAP."

Sternberg pointed out that the toxicity profiles were quite different in the two trials. The AAP results are consistent with the LATITUDE trial, which also favoured AAP over standard of care in high risk patients. (5)

She said: “Both STAMPEDE randomised trials support starting hormonal therapy plus either AAP or six cycles of docetaxel. At one and two years, the percentage of patients with grade 3 or 4 (severe) toxicities was low and similar among the two groups. Toxicities associated with chemotherapy for six cycles will dominate decisions about upfront docetaxel. Toxicities associated with AAP are also likely to influence decisions. Physicians will base their choice of therapy on availability and patient characteristics and preferences.”

Regarding the need for further studies, Sternberg said: “Cardiovascular follow-up will be important in patients taking AAP. In the future, we will get data on whether patients could start with both docetaxel and novel hormonal therapy such as AAP. Ongoing randomised trials in metastatic hormone sensitive prostate cancer will evaluate the combination of novel hormonal therapy and chemotherapy upfront (ARASENS; NCT02799602) as will data from the PEACE 1 trial (NCT01957436) in which two-thirds of patients will receive AAP plus docetaxel chemotherapy for hormone sensitive high risk prostate cancer.”

Further research on abiraterone in patients with high risk prostate cancer will be presented on Friday, 8 September. (6) STAMPEDE contributes substantially to the network meta-analysis presented on Sunday, 10 September by Dr CL Vale. (7)

-END-

Notes to Editors

Please make sure to use the official name of the meeting in your reports: ESMO 2017 Congress

References

  1. Abstract LBA31_PR ‘Adding abiraterone acetate plus prednisolone (AAP) or docetaxel for patients (pts) with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): directly randomised data from STAMPEDE (NCT00268476)‘ will be presented by Mr Matthew Sydes during Proffered Paper Session ‘Genitourinary tumours, prostate’ on Friday, 8 September 2017, 14:00 to 15:30 (CEST) in the Sevilla Auditorium.
  2. James ND, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–1177. doi: 10.1016/S0140-6736(15)01037-5. Epub 2015 Dec 21.
  3. James ND, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med . 2017;377:338–351. doi: 10.1056/NEJMoa1702900. Epub 2017 Jun 3.
  4. HR<1 favours abiraterone; HR>1 favours docetaxel
  5. Fizazi K, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med .  2017;377(4):352–360. doi: 10.1056/NEJMoa1704174.
  6. Abstract 783O ‘Benefits of Abiraterone Acetate Plus Prednisone (AA+P) When Added to Androgen Deprivation Therapy (ADT) in LATITUDE on Patient (Pt) Reported Outcomes (PRO)‘ will be presented by Dr Kim Chi during Proffered Paper Session ‘Genitourinary tumours, prostate’ on Friday, 8 September 2017, 14:00 to 15:30 (CEST) in the Sevilla Auditorium.
  7. Abstract LBA33 ‘What are the optimal systemic treatments for men with metastatic, hormone-sensitive prostate cancer? A STOPCaP systematic review and network meta-analysis’ will be presented by Dr CL Vale during Poster Discussion Session ‘Genitourinary tumours, prostate’ on Sunday, 10 September 2017, 09:15 to 10:30 (CEST) in the Bilbao Auditorium.

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Abstract LBA31_PR

Adding abiraterone acetate plus prednisolone (AAP) or docetaxel for patients (pts) with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): directly randomised data from STAMPEDE (NCT00268476)

M.R. Sydes1, M.D. Mason2, M.R. Spears3, N.W. Clarke4, D. Dearnaley5, A.W.S. Ritchie6, M. Russell7, C. Gilson1, R. Jones7, J. de Bono8, S. Gillessen9, R. Millman10, S. Tolan11, J. Wagstaff12, S. Chowdhury13, J. Lester14, D. Sheehan15, J. Gale16, M.K. Parmar3, N.D. James17
1Institute of Clinical Trials and Methodology, MRC Clinical Trials Unit at UCL, London, UK, 2School of Medicine, Cardiff University, Cardiff, UK, 3MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK, 4Oncology, Royal Salford NHS Foundation Trust, M Hd, UK, 5Oncology, Institute of Cancer Research Royal Marsden Hospital, Sutton, UK, 6MRC Clinical Trials Unit, University College London, London, UK, 7Oncology, University of Glasgow, Glasgow, UK, 8Section of Medicine, Institute of Cancer Research Royal Marsden Hospital, Sutton, UK, 9Dept of Medical Oncology, Kantonsspital, Switzerland, Switzerland, 10Clinical Trials Unit, MRC, Wcb Nh, UK, 11Oncology, Clatterbridge Oncology Centre, Wirral, UK, 12Medical Oncology, South West Wales Cancer Institute, Singleton Hospital, Swansea, UK, 13Medical Oncology, Guy's and St. Thomas' Hospital NHS Trust, London, UK, 14Oncology, Velindre, Wales, UK, 15Urology, Royal Devon & Exeter Hospital NHS Foundation Trust, Exeter, UK, 16Oncology, Queen Alexandra Hospital, Portsmouth, UK, 17Oncology, Queen Elizabeth-University Hospital Birmingham NHS Foundation Trust, Birmingham, UK

Background: Adding abiraterone acetate + prednisone (AAP) & adding docetaxel + prednisone (DocP) to standard of care (SOC) each improved survival vs SOC in STAMPEDE: a multi-arm multi-stage platform randomised controlled protocol recruiting pts with high risk locally advanced or metastatic PCa starting long-term ADT. We share the first direct, randomised data of SOC+AAP or SOC+DocP using a STAMPEDE subset.

Methods: Recruitment to the “DocP comparison” & “AAP comparison” overlapped Nov2011 - Jan2014. SOC was long term ADT or 2+yr ADT with RT (for some M0). Stratified randomisation allocated pts 2:1:2 to SOC : or SOC + Doc 75mg/m2 3-weekly x6 + P 5mg twice daily : or SOC + AA 1000mg + P 5mg daily. AAP duration depended on stage & intent for radical RT. Primary outcome measure was death from any cause. Analyses used Cox proportional hazards & flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison; power is limited, but is indicative of the likely magnitude of difference: HR<1 favours SOC+AAP, HR>1 favours SOC+DocP. All confidence intervals (CI) are 95%.

Results: 566 pts were contemporaneously randomised: 189 SOC+DocP (the last of 592 SOC+DocP pts) & 377 SOC+AAP (the first of 960 SOC+AAP pts). Groups were well balanced with 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO PS 0; median age 66yr & PSA 56ng/ml. At median follow up 4 yr, there were 149 deaths (45 SOC+Doc, 111 SOC+AAP): survival HR 1.16 (0.82-1.65); failure free survival HR= 0.51 (0.39-0.67); progression free survival HR 0.65 (0.48-0.88); metastases free survival HR 0.77 (0.57-1.03); & SRE HR 0.83 (0.55-1.25). There was no heterogeneity by baseline M0/M1. Grade 3, 4, 5 toxicity was 36%, 13%, 1% SOC+DocP, & 40%, 7%, 1% SOC+AAP. Subsequent treatments varied by arm, with much crossing after progression.

Conclusions: In this direct, randomised, comparative analysis of 2 new standards for HNPC, FFS & PFS clearly favoured SOC+AAP &, with less certainty, MFS & SRE favoured SOC+AAP & survival SOC+Doc. Worst toxicity grade was similar. Drug availability may drive treatment choice. Published STAMPEDE data also contribute to a network MA (#2871).

Clinical trial identification: NCT00268476 STAMPEDE

Legal entity responsible for the study: Medical Research Council

Funding: Cancer Research UK, Medical Research Council, Janssen; Astellas, Clovis Oncology, Novartis, Pfizer, Sanofi-Aventis

Disclosure: M.R. Sydes: Mr. Sydes reports grants and non-financial support from Janssen, Astellas, Clovis Oncology, Novartis, Pfizer, Sanofi-Aventis
 M.D. Mason: Prof Mason reports personal fees and other from Sanofi, personal fees from Bayer, other from Janssen, outside the submitted work
 N.W. Clarke: Dr. clarke reports personal fees from Janssen Pharmaceuticals, during the conduct of the study; personal fees from Janssen Pharmaceuticals, outside the submitted work; .
 D. Dearnaley: Financial Support for Trial Recruitment
 M. Russell: Dr. Russell reports from Jannsen-Cilag, outside the submitted work.
 R. Jones: Dr. Jones reports personal fees and non-financial support from Janssen, grants, personal fees and other from Astellas, outside the submitted work .
 J. de Bono: I am an employee of the ICR which has a commercial interest in abiraterone. I have served on Janssen Advisory Board as a consultant
 S. Gillessen: Bayer, CureVac, Janssen Cilag, Dendreon Corp, Astellas, Millennium Pharmaceuticals, Orion, Sanofi, MaxiVax SA, AAA, Bristol-Myers Squibb, Ferring, Roche, Innocrin Pharmaceuticals, NEKTAR THERAPEUTICS, ProteoMedix
 S. Chowdhury: Dr. Chowdhury reports personal fees from Janssen Paharmaceutical, outside the submitted work; .
 J. Lester: Dr. Lester reports personal fees, non-financial support and other from Janssen, personal fees, non-financial support and other from Astellas, outside the submitted work
 M.K. Parmar: Jansenn: Unrestricted grant to contribute to this comparison of STAMPEDE which supports the protocol overall, plus abiraterone and distribution.
 N.D. James: Dr. James reports grants, personal fees and non-financial support from Janssen, Astellas, Sanofi, Novartis during the conduct of the study; grants and non-financial support from Clovis Oncology, Pfizer
 All other authors have declared no conflicts of interest.

Keywords: ADT+docetaxel, randomised comparison, hormone-dependent cancers, abiraterone

Abstract 783O

Benefits of Abiraterone Acetate Plus Prednisone (AA+P) When Added to Androgen Deprivation Therapy (ADT) in LATITUDE on Patient (Pt) Reported Outcomes (PRO)

K. Chi1, A. Protheroe2, A. Rodriguez Antolin3, G. Facchini4, H. Suttmann5, N. Matsubara6, Z.-Q. Ye7, B. Keam8, T. Li9, K. McQuarrie10, B. Jia11, P. De Porre12, J. Martin13, M.B. Todd14, K. Fizazi15
1Clinical Trials Unit, BC Cancer Agency, Vancouver, British Columbia/CANADA, 2Oncology, The Churchill Hospital Oxford University Hospitals NHS Trust, Oxford/UNITED KINGDOM, 3Urology, Hospital Universitario 12 de Octubre, Madrid/SPAIN, 4Uro-gynecological, Istituto Nazionale Tumori – I.R.C.C.S. - Fondazione Pascale, Naples/ITALY, 5Urology, Urologikum Hamburg, Hamburg/GERMANY, 6Division Of Breast And Medical Oncology, National Cancer Center Hospital East, Kashiwa/JAPAN, 7Urology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan/CHINA, 8Genitourinary, Seoul National University Hospital, Seoul/KOREA, REPUBLIC OF, 9Global Market Access Oncology, Janssen Global Services, Raritan/UNITED STATES OF AMERICA, 10Patient Reported Outcome Group, Janssen Research & Development, Horsham/UNITED STATES OF AMERICA, 11Biostatistics, Janssen Research & Development, Shanghai/CHINA, 12Clinical Oncology, Janssen Research & Development, Beerse/BELGIUM, 13Clinical Oncology, Janssen Research & Development, Buckinghamshire/UNITED KINGDOM, 14Oncology, Janssen Global Services, Raritan/UNITED STATES OF AMERICA, 15Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif/FRANCE

Background: In the LATITUDE study, treatment with ADT+AA+P significantly improved overall survival and delayed disease progression in pts with newly diagnosed, high-risk, metastatic castration-naïve prostate cancer (mCNPC). In this analysis we evaluated the impact of ADT+AA+P on PROs, including symptom and health-related quality of life (HRQoL) measures.

Methods: 1199 mCNPC pts were randomized 1:1 to ADT + AA+P or ADT + placebos (PBOs). Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EQ-5D-5L questionnaires were administered at baseline (BL), Day 1 of Cycles (C) 2-13, then every 2 months until treatment discontinuation (TD). EQ-5D-5L were performed every 4 months until 12 months after TD. Time to event and repeated measures analyses on changes from baseline were conducted.

Results: Questionnaire compliance rate was high at ≥ 90%. Compared to ADT+PBOs, the ADT+AA+P arm had significant delayed time to pain and fatigue intensity and interference progression (Table). FACT-P assessments demonstrated significant delay in degradation for the total score and symptom subscales for the ADT+AA+P arm (Table). Repeated measures analyses showed maintenance or improvement from BL for the ADT+AA+P arm compared to the ADT+PBOs arm, with significant differences emerging as early as C2. Significant improvement from BL in EQ-5D VAS for general health status and health utility scores occurred as early as C5 and was maintained throughout the study.

Time to Progression and Relative Risk for HRQoL End Points

Measure ADT+AA+P
 (months)
ADT+PBOs (months) HR (95% CI) p Value
Median time to worst pain intensity progression (BPI-SF) NR 16.6 0.695
 (0.583-0.829)
< 0.001
Median time to pain interference progression (BPI-SF) NR 18.4 0.671
 (0.561-0.803)
< 0.001
Median time to fatigue intensity progression (BFI) NR NR 0.652
 (0.527-0.805)
< 0.001
Median time to fatigue interference progression (BFI) NR NR 0.594 (0.470-0.750) < 0.001
Median time to FACT-P degradation - - - -
Total Score 12.9 8.3 0.853
 (0.736-0.989)
0.032
Pain-related Subscale 10.2 6.5 0.760
 (0.659-0.876)
< 0.001
Prostate Cancer Subscale 8.3 5.6 0.808
 (0.701-0.930)
0.003

HR, hazard ratio; CI, confidence interval.

Conclusions: Compared with ADT+PBOs, treatment with ADT+AA+P consistently demonstrated improvement across multiple PRO measures, with statistically significant improvement in HRQoL and delays in progression of pain fatigue intensity and interference, and functional decline. Results for PROs were consistent with improvements in clinical outcomes.
Clinical trial identification: EudraCT: 2012-002940-26 NCT01715285

Keywords: patient reported outcomes, abiraterone acetate, abiraterone, prostate cancer, metastatic castration-naive prostate cancer

Funding: Janssen Research & Development

Disclosure: K. Chi: Consulting/Advisory Role: Janssen Research Funding: Janssen
 A. Protheroe: Consulting/Advisory Role: IPSEN, Bayer, Roche, BMS Research Funding: Merck Travel, Accommodations, Expenses: BMS
 A. Rodriguez Antolin: Consulting/Advisory Role: Astellas, Janssen, Bayer Speaker's Bureau: Astellas, Janssen Travel, Accommodations, Expenses: Astellas, IPSEN Pharma
 H. Suttmann: Honoraria, Consulting/Advisory Role, Research Funding: Astellas, Bayer Health Care, Bristol-Myers-Squibb, Ipsen, Janssen-Cilag, Medac, Santorin-Aventis
 N. Matsubara: Consulting/Adisory Role: MSD,AstraZeneca,Eisai,Ono,Kissei,Sanofi,Taiho,Takeda,Chugai,Novartis,Bayer, Yakuhin, Pfizer Japan, Merck, Serono, Janssen - Research Funding: Shionogi,Bayer,Yakuhin,Janssen,Chugai, Eli Lilly Japan,Eisai,MSD
 Z. Ye: Consulting/Adisory Role: MSD,AstraZeneca,Eisai,Ono,Kissei,Sanofi,Taiho,Takeda,Chugai,Novartis,Bayer, Yakuhin, Pfizer Japan, Merck, Serono, Janssen - Research Funding: Shionogi,Bayer,Yakuhin,Janssen,Chugai, Eli Lilly Japan,Eisai,MSD
 T. Li, P. De Porre, J. Martin: Employment at Janssen Research and Development Stock Ownership of Johnson & Johnson
 K. McQuarrie, B. Jia, M.B. Todd: Employment at Janssen Research and Development Stock Ownership of Johnson & Johnson
 K. Fizazi: Honoraria, Consulting/Advisory Role: Astellas, Bayer, Clovis, Curevac, Genentech, Janssen, Orion, Sanofi
 All other authors have declared no conflicts of interest.

Abstract LBA33

What are the optimal systemic treatments for men with metastatic, hormone-sensitive prostate cancer? A STOPCaP systematic review and network meta-analysis

C.L. Vale1, D.J. Fisher1, J. Carpenter1, I.R. White1, S. Burdett1, N.W. Clarke2, K. Fizazi3, G. Gravis4, N.D. James5, M.D. Mason6, M.K. Parmar1, L.H. Rydzewska1, C.J. Sweeney7, M.R. Spears1, M.R. Sydes1, J.F. Tierney1
1MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK, 2Dept of Oncology, Royal Salford NHS Foundation Trust, Salford, UK, 3Dept of Cancer Medicine, Gustave Roussy, Villejuif, France, 4Dept of Medical Oncology, Institute Paoli Calmettes, Marseille, France, 5Clinical Trials Unit, The Institute of Cancer and Genomic Sciences, Birmingham, UK, 6School of Medicine, Cardiff University, Cardiff, UK, 7Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

Background: Our prior STOPCaP systematic reviews showed improved survival for men with metastatic hormone-sensitive prostate cancer (mHSPC) when abiraterone acetate plus prednisolone/prednisone (AAP) or docetaxel (DOC), but not zoledronic acid (ZA), were added to androgen deprivation therapy (ADT). Trial evidence also suggests a benefit of combining celecoxib (CEL) with ZA and ADT. To establish the optimal treatments, a network meta-analysis (NMA) was performed based on aggregate data (AD) from all available studies.

Methods: Overall survival (OS) data from completed reviews of DOC, ZA and AAP and from recent trials of ZA and CEL contribute to this new comprehensive AD-NMA. Correlations between treatment comparisons within multi-arm multi-stage (MAMS) trials (e.g. STAMPEDE) were estimated from control-arm event counts in overlapping recruitment periods. We assumed network consistency and a common heterogeneity variance.

Results: Network estimates of effects on OS were consistent with reported comparisons with ADT alone for: AAP (HR=0.61, 95% CI 0.51-0.76); DOC (HR=0.74, 95% CI 0.65-0.85); CEL+ZA (HR=0.77 95%CI 0.62-0.96) and DOC+ZA (HR=0.78 95% CI 0.65-0.93). The effect of CEL+ZA is consistent with the additive effects of the individual treatments. Based on the current data, the network OS results suggest that AAP has the highest probability of being best, and DOC second-best. ADT, ZA and CEL have the highest probability of being worst. Results for failure-free survival will be presented.

Conclusions: Uniquely, we have included all available results and appropriately accounted for inclusion of MAMS trials in this AD-NMA. Our results clearly support the use of AAP or DOC with ADT in men with mHSPC; direct evidence from the STAMPEDE trial (Abstract #3632) and the ongoing PEACE-1 trial (NCT01957436) will corroborate (or otherwise) their relative effects. A NMA based on individual participant data is in development to fully account for patient variability across trials, changes in prognosis or treatment effects over time, and the potential impact of treatment on progression.

Legal entity responsible for the study: University College London

Funding: UK Medical Research Council

Disclosure: J. Carpenter: Funded by the MRC, HEFCE and contributions from NIHR, ESRC, MRC and EU funds. He undertakes methodological consultancy work for Novartis and GlaxoSmithKline, and has given courses for GlaxoSmithKline, Bayer and Boehringer.
 N.W. Clarke: Advisory Boards: Astellas, Janssen, Ferring, Bayer, AstraZeneca; Corporate-sponsored Research: AstraZeneca.
 K. Fizazi: Advisory boards for Sanofi and Novartis.
 G. Gravis: Travel grants from Sanofi, Astellas and Janssen.
 N.D. James: Grants, personal fees and non-financial support from Janssen, Astellas, Sanofi, Novartis during the conduct of the study; grants and non-financial support from Clovis Oncology, Pfizer
 M.D. Mason: Delivering a paid lecture for Janssen and has been an advisory board member for Sanofi and Bayer.
 M.K. Parmar: Grants from Astellas, Janssen, Novartis, Pfizer, Sanofi and Clovis Oncology
 C.J. Sweeney: Ownership BIND; Advisory board Astellas/Medivation, Astra Zeneca, Sanofi, Janssen, BIND, Bayer; Grants Janssen, Astellas/Medivation, Sanofi, Janssen, Soti , Exelixis; Consultancy Astellas/Medivation, Pfizer, Sanofi, Janssen, BIND, Bayer, Genentech.
 M.R. Spears, M.R. Sydes: Grants from Astellas, Janssen, Novartis, Pfizer, Sanofi and Clovis Oncology.
 All other authors have declared no conflicts of interest.

Keywords: prostate cancer, network meta analysis, systematic review, systemic therapy