611O - Abiraterone acetate plus prednisolone for hormone-naïve prostate cancer (PCa): Long-term results from metastatic (M1) patients in the STAMPEDE randomised trial (NCT00268476)

Background

Abiraterone acetate plus prednisolone previously showed a clear survival advantage in men starting long-term hormone therapy for prostate cancer in STAMPEDE, a randomized controlled trial using a multi-arm multi-stage platform design. STAMPEDE included a wide range of men with M1 or M0 disease. The LATITUDE trial, in patients with high-burden M1 disease only, reported a similar magnitude of effect to the comparable subset of STAMPEDE pts. We report long-term outcomes in the M1 subset of pts in STAMPEDE.

Methods

All patients received androgen deprivation therapy (ADT). Stratified randomization allocated pts 1:1 to ADT alone or adding daily abiraterone acetate 1000mg + prednisolone 5mg (SOC+AAP) continued until PSA, radiological & clinical progression. The primary outcome measure was death from any cause. The data freeze for this long-term analysis was planned for 3yr after the primary survival results when a meaningful increase in data was anticipated. Analyses used Cox proportional hazards & flexible parametric models, adjusted for baseline stratification factors.

Results

Of 1,917 pts contemporaneously randomized to these groups (Nov-2011 to Jan-2014), 1,003 (52%) had M1 disease. The M1 groups were balanced: median age 67yr; 48% high-burden, 44% low-burden, 8% burden not assessable; 94% newly-diagnosed; median PSA 97ng/ml. Median follow-up had increased from 3.5yr to 6.1yr & number of ADT-only deaths increased by 50%, from 218 previously to 329. With 244 ADT+AAP deaths, the adjusted HR=0·60 (95%CI 0·50—0·71; p=0.31x10^-9) favouring ADT+AAP, with 5-yr survival improved from 41% ADT-only to 60% ADT+AAP. The relative effect of abiraterone was similar in low-burden (HR=0·55; 95%CI 0·41—0·76) and high-burden (HR=0·54; 95%CI 0·43—0·69) patients. Median time on ADT+AAP was 2.4yr, with a current maximum of 8.1yr. Toxicity at 4yr post-randomisation was similar, with 16% of patients in each group reporting grade 3 or higher toxicity.

Conclusions

A sustained and substantial improvement in overall survival of M1 prostate cancer patients was achieved with ADT + abiraterone acetate + prednisolone, irrespective of burden of disease.

Clinical trial identification

NCT00268476.

Editorial acknowledgement

Legal entity responsible for the study

UCL and the STAMPEDE investigators.

Funding

Janssen; Astellas, Clovis, Novartis, Pfizer, Sanofi Aventis.

Disclosure

N. James: Advisory/Consultancy, Advisory Board: Sanofi; Advisory/Consultancy, Advisory Board: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Advisory Board, speaker fees, assistance with travel: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Advisory Board, speaker fees, assistance with travel: Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Advisory Board, speaker fees, assistance with travel: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Advisory Board, speaker fees, assistance with travel: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Advisory Board, speaker fees, assistance with travel: AstraZeneca. N. Clarke: Advisory/Consultancy, Consultation and advisory fees: Janssen; Advisory/Consultancy, Consultation/ Lecture fees: Astellas; Advisory/Consultancy, Consultation / Advisory fees: Bayer. G. Attard: Speaker Bureau/Expert testimony, Speakers' bureaus: Sanofi Aventis. D. Dearnaley: Research grant/Funding (institution), C46/A3976, C46/A10588 and C33589/A19727. : Cancer Research UK; Research grant/Funding (self), Consultant and Advisory Board Honoraria: Takeda; Research grant/Funding (self), Consultant and Advisory Board Honoraria: Amgen; Research grant/Funding (self), Consultant and Advisory Board Honoraria: Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses, Advisory Board, Travel, Accommodation: Sandoz; Advisory/Consultancy, Travel/Accommodation/Expenses, Financial support for trial recruitment, Advisory Board, Speakers Bureau, Travel and Accommodation: Janssen. S. Gillessen: Honoraria (institution), Honorarium payments to hospital: Bayer; Honoraria (institution), Honorarium payments to hospital: Curevac; Honoraria (self), Honoraria (institution), Honorarium payments to hospital: Janssen; Honoraria (institution), Honorarium payments to hospital: Astellas; Honoraria (self), Honoraria (institution), Honorarium payments to hospital: Orion; Honoraria (institution), Honorarium payments to hospital: Max/Vax SA; Honoraria (institution), Honorarium payments to hospital: Ferring; Honoraria (institution), Honorarium payments to hospital: Roche; Honoraria (institution), Honorarium payments to hospital: Innocrin Pharmaceuticals; Honoraria (self), Honorarium payments to hospital: Sanofi; Honoraria (institution), Honorarium payments to hospital: Novartis; Non-remunerated activity/ies, Uncompensated advisory role: Nectar Therapeutics; Non-remunerated activity/ies, Uncompensated advisory role: ProteoMedix; Honoraria (institution), Honorarium payments to hospital: Cell Search; Honoraria (institution), Honorarium payments to hospital: Clovis; Honoraria (institution), Honorarium payments to hospital: Bristol-Myers Squibb; Honoraria (institution), Honorarium payments to hospital: MSD Merck Sharp & Dome. A. Birtle: Honoraria (self), Advisory/Consultancy, Advisory Board Honoraria: Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, Speaker Fee + Advisory Board Honoraria: Sanofi; Honoraria (self), Advisory/Consultancy, Advisory Board Honoraria: Janssen; Advisory/Consultancy, Advisory Board Honoraria: Bayer; Advisory/Consultancy, Advisory Board Honoraria: Astra Zeneca. S. Chowdhury: Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Honoraria, Speakers fee, Travel Grant: Janssen. Z. Malik: Advisory/Consultancy, Advisory boards: Sanofi; Advisory/Consultancy, Advisory boards: Janssen; Advisory/Consultancy, Advisory boards: Pfizer; Travel/Accommodation/Expenses, Assisted travel to Congress: Bayer. J. O'Sullivan: Advisory/Consultancy, Speaker Bureau/Expert testimony, Ad boards + Speakers fees: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Ad boards + Speakers fees: Atellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, Ad boards + Speakers fees: Bayer. C. Pezaro: Honoraria (self), Honoraria (institution): Astellas; Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Honoraria (institution): Janssen; Honoraria (self), Honoraria (institution): Mundipharma; Honoraria (self), Honoraria (institution): Pfizer; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Janssen. D. Sheehan: Travel/Accommodation/Expenses, Sponsorship for meeting attendance: Astellas; Travel/Accommodation/Expenses, Sponsorship for meeting attendance: Ipsen. J. Tanguay: Travel/Accommodation/Expenses, Conference attendance: Roche; Travel/Accommodation/Expenses, Conference attendance: Janssen; Advisory/Consultancy, Advisory board: Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses, Advisory board & conference attendance: Bayer; Advisory/Consultancy, Advisory board: AstraZeneca. M.K. Parmar: Research grant/Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Astellas; Research grant/Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Clovis; Research grant/Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Novartis; Research grant/Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Pfizer; Research grant/Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Sanofi. M.R. Sydes: Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Clovis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Sanofi-Aventis; Honoraria (self): Eli-Lilly. All other authors have declared no conflicts of interest.