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Proffered Paper session: GU tumours, prostate

1358O - Clinical qualification of transcriptome signatures for advanced prostate cancer (APC) starting androgen deprivation therapy (ADT) with or without abiraterone acetate and prednisolone (AAP): An ancillary study of the STAMPEDE AAP trial

Date

11 Sep 2022

Session

Proffered Paper session: GU tumours, prostate

Topics

Translational Research

Tumour Site

Prostate Cancer

Presenters

Marina Parry

Citation

Annals of Oncology (2022) 33 (suppl_7): S616-S652. 10.1016/annonc/annonc1070

Authors

M. Parry1, E. Grist1, C.D. Brawley2, J.A. Proudfoot3, L. Mendes1, S. Lall1, A.P. Hoyle4, A. Sachdeva5, Y. Liu3, C.L. Amos6, M.R. Sydes7, R.J. Jones8, M.K. Parmar9, F. Feng10, C.J. Sweeney11, N. Clarke12, E. Davicioni3, N.D. James13, L.C. Brown14, G. Attard1

Author affiliations

  • 1 Oncology Department - Treatment Resistance, UCL Cancer Institute - Paul O'Gorman Building, WC1E 6DD - London/GB
  • 2 Mrc Ctu Department, Medical Research Council Clinical Trials Unit, WC1V 6LJ - London/GB
  • 3 Urology, Veracyte, Inc. - Headquarters, 94080 - South San Francisco/US
  • 4 Uro-oncology Dept., The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 5 Department Of Surgery, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 6 Mrc Clinical Trials Unit, Cancer Research UK & University College London Cancer Trials Centre, W1T 4TJ - London/GB
  • 7 Mrc Clinical Trials Unit At Ucl, Medical Research Council Clinical Trials Unit, WC1V 6LJ - London/GB
  • 8 Institute Of Cancer Sciences, MVLS - Medical, Veterinary and Life Sciences College - University of Glasgow, G12 8QQ - Glasgow/GB
  • 9 Mrc Clinical Trials Unit, Institute of Clinical Trials and Methodology-UCL, WC2B 6NH - London/GB
  • 10 Department Of Radiation Oncology, JLABS @ MBC BioLabs, 94107 - San Francisco/US
  • 11 Medical Oncology Department, Dana Farber Cancer Institute, 02115 - Boston/US
  • 12 Division Of Cancer Sciences, The University of Manchester, M13 9PL - Manchester/GB
  • 13 Prostate And Bladder Cancer Research Department, ICR - Institute of Cancer Research, SW7 3RP - London/GB
  • 14 Mrc Clinical Trials Unit, MRC - Medical Research Council Clinical Trials Unit - University College London (UCL), WC1V 6LJ - London/GB
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Resources

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Abstract 1358O

Background

Addition of AAP to ADT is standard of care for APC (metastatic, M1 and high-risk non-metastatic, M0). We tested transcriptome signatures as prognostic and predictive biomarkers for patients (pt) starting ADT +/- AAP.

Methods

Whole transcriptome profiling was performed using a clinical test (Decipher, Veracyte, San Diego) on tumor index core mRNA from pt randomised 1:1 ADT:ADT+AAP in STAMPEDE. A pre-specified statistical analysis plan was approved by the trial oversight groups. Cox models were fit with mRNA signature, AAP (+/-), age, WHO PS, pre-ADT PSA, NSAIDs/aspirin use, Gleason score, and disease burden (M0N0 vs M0N1 vs M1 low volume vs M1 high volume) as covariates. Primary analyses included Decipher genomic classifier (GC, continuous) for prognosis and AR-activity (AR-A, average vs low) for prediction. AAP trial closed to follow up Nov 2021.

Results

Of 1917 pt (full trial cohort, FTC) enrolled Nov 2011 - Jan 2014, 1824 consented to tumor analysis; 1298 (71%) reviewed centrally, 974 (75%) gave transcriptomes; 781 (80%) passed QC. Of 781, 50% vs 52% in FTC were M1; other clinical variables, well balanced. Median follow-up = 94 months (IQR: 84 - 97). GC was strongly prognostic in APC (per 0.1 increment, M1 OS (HR [95% CI] 1.17 [1.09 - 1.26], p < 0.001), M0 MFS (HR 1.20 [1.09 - 1.31], p < 0.001), Table. AR-A showed no interaction with AAP (interaction HR 0.86 [0.56 - 1.33], p = 0.5). Secondary analyses showed consistent effect of AAP across PAM50, PSC and GC and worse outcome for low AR-A (M1, OS HR: 1.30 [0.99 - 1.70], p = 0.06; M0, MFS HR: 1.56 [1.08 - 2.27], p = 0.02). Table: 1358O

Baseline met status Treatment Decipher GC End-point Free of an event at 72 months
M1 ADT >median OS 17%
ADT + AAP >median OS 43%
ADT ≤median OS 51%
ADT + AAP ≤median OS 64%
M0 ADT >median MFS 53%
ADT + AAP >median MFS 66%
ADT ≤median MFS 81%
ADT + AAP ≤median MFS 85%

Conclusions

Decipher GC is strongly prognostic in APC treated with ADT +/- AAP. AAP effect is consistent across AR-A, PAM50, PSC and GC categories but absolute benefit varied. We clinically qualify mRNA signatures for potential use in treatment intensification/de-intensification of pt treated with ADT + AAP.

Clinical trial identification

NCT00268476, ISRCTN78818544.

Editorial acknowledgement

Legal entity responsible for the study

Medical Research Council Clinical Trials Unit at University College London.

Funding

Prostate Cancer UK, Prostate Cancer Foundation, Cancer Research UK, Medical Research Council, Janssen, Veracyte.

Disclosure

J.A. Proudfoot: Financial Interests, Personal, Full or part-time Employment: Veracyte Inc.; Financial Interests, Personal, Stocks/Shares: Veracyte, Inc. Y. Liu: Financial Interests, Personal, Full or part-time Employment: Veracyte; Financial Interests, Personal, Stocks/Shares: Veracyte, Inc. 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, Janssen, Novartis, Pfizer, Sanofi; Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology. R. Jones: Financial Interests, Personal, Advisory Board, advisory board attendance: AstraZeneca, Astellas; Financial Interests, Personal, Invited Speaker, Honoraria for speaking: Astellas; Financial Interests, Personal, Advisory Board: Bayer, Clovis, Exelixis, Ipsen, Bristol Myers Squipp, Merck Serono, Merck Sharpe Dome, Roche, Janssen, Novartis / AAA; Financial Interests, Personal, Invited Speaker: Bayer, Ipsen, Bristol Myers Squibb, Merck Serono, Merck Sharpe Dome, Pfizer, Roche, Janssen; Financial Interests, Institutional, Other, IDMC membership: Roche; Financial Interests, Institutional, Other, IDMC member: Stab; Financial Interests, Institutional, Invited Speaker: Janssen, Pfizer, Tail, AstraZeneca, BioXcel, Bristol Myers Squibb, Novartis/AAA, Roche, MSK. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL; Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis; Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London; Non-Financial Interests, Advisory Role, rEECur: University of Birmingham; Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham. F. Feng: Financial Interests, Personal, Advisory Role: Astellas, Bayer, BMS, Foundation Medicine, Janssen, Myovant, Novartis, Roivant; Financial Interests, Personal, Advisory Board: Artera, BlueStar Genomics, SerImmune. C.J. Sweeney: Financial Interests, Personal, Advisory Board, Consultancy: Genentech, Roche, Bayer, Astellas, Pfizer, Pfizer, Sanofi, Lilly; Financial Interests, Personal, Other, Consultancy: Janssen; Financial Interests, Personal, Stocks/Shares: Leuchemix; Financial Interests, Institutional, Research Grant: Bayer, Janssen, Astellas, Pfizer, Dendreon, Sanofi. N. Clarke: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca, Astellas, Janssen, Bayer; Financial Interests, Personal, Speaker’s Bureau: Janssen, AstraZeneca, Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Pfizer, NICE; Financial Interests, Personal, Funding: AstraZeneca, Astellas, Janssen, Bayer. E. Davicioni: Financial Interests, Personal, Full or part-time Employment: Veracyte Inc.; Financial Interests, Personal, Stocks/Shares: Veracyte, Inc. N.D. James: Financial Interests, Personal, Funding: Sanofi, Novartis, Janssen, Astellas, Bayer. L. Brown: Financial Interests, Institutional, Research Grant, £170k Educational Grant for the FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca; Financial Interests, Institutional, Funding, Various Grants Awarded to my Institution for Work Undertaken as Part of the STAMPEDE Trial: Janssen Pharmaceuticals; Non-Financial Interests, Other, I am a Member of the CRUK CERP Funding Advisory Panel and my Institution also receive grant funding from CRUK for the STAMPEDE and FOCUS4 trials: Cancer Research UK. G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion; Financial Interests, Personal, Royalties, Included in List of Rewards to Discoverers of Abiraterone: Institute of Cancer Research; Financial Interests, Institutional, Research Grant: Janssen, Astellas; Non-Financial Interests, Principal Investigator: Janssen, Astellas; Non-Financial Interests, Advisory Role: Janssen, AstraZeneca. All other authors have declared no conflicts of interest.

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