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ePoster Display

604P - Predictive genomic biomarkers in non-metastatic castration resistant prostate cancer (nmCRPC) treated with androgen receptor pathway inhibitors (ARPi)

Date

16 Sep 2021

Session

ePoster Display

Topics

Clinical Research;  Targeted Therapy;  Translational Research;  Pathology/Molecular Biology

Tumour Site

Prostate Cancer

Presenters

Richard Gagnon

Citation

Annals of Oncology (2021) 32 (suppl_5): S626-S677. 10.1016/annonc/annonc702

Authors

R. Gagnon1, S.E. El Hallani2, R. Lee-Ying3, M.P. Kolinsky4, D.J. Khalaf5, S. Cook6, C. Vasquez7, D. Samuel8, J.D. Lewis9, R.M. Faridi10, M. Borkar11, D.Y.C. Heng12, N. Alimohamed13, J..D. Ruether3, G.T. Gotto14, A. Fairey15, T.A. Bismar16, S. Yip1

Author affiliations

  • 1 Oncology, University of Calgary, T3c 2z1 - Calgary/CA
  • 2 Pathology And Lab Medicine, University of Alberta, T5H 3V9 - Edmonton/CA
  • 3 Medical Oncology Department, Tom Baker Cancer Centre, T2N 4N2 - Calgary/CA
  • 4 Oncology, University of Alberta Cross Cancer Institute, T6G 1Z2 - Edmonton/CA
  • 5 Medical Oncology Dept., BC Cancer Agency - Vancouver, V5Z 4E6 - Vancouver/CA
  • 6 Medicine, University of Calgary, T2N 2T9 - Calgary/CA
  • 7 Oncology, University of Alberta, T6G 2R3 - Edmonton/CA
  • 8 Molecular Pathology, University of Calgary, T2N 1N4 - Calgary/CA
  • 9 Experimental Oncology, University of Alberta, T6G2E1 - Edmonton/CA
  • 10 Pathology And Laboratory Medicine, Faculty of Medicine, University of Calgary, T2V 4T9 - Calgary/CA
  • 11 Alberta Transplant Institute, University of Calgary, T2N 1N4 - Calgary/CA
  • 12 Oncology Department, Tom Baker Cancer Centre, T2N 4N2 - Calgary/CA
  • 13 Oncology, Tom Baker Cancer Centre, T2N 4N2 - Calgary/CA
  • 14 Department Of Surgery, University Of Calgary, Southern Alberta Institute of Urology, T2V1P9 - Calgary/CA
  • 15 Urology, University of Alberta, T6G 1Z1 - Edmonton/CA
  • 16 Pathology And Lab Medicine, Faculty of Medicine, University of Calgary, T2V 4T9 - Calgary/CA

Resources

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Abstract 604P

Background

Although recent trials have demonstrated overall survival (OS) and metastasis free survival (MFS) benefit with the use of ARPi in high-risk nmCRPC, individual treatment outcomes may vary. This retrospective multicentre analysis explores the association between genomic mutations with ARPi treatment outcomes in nmCRPC patients to identify predictive biomarkers.

Methods

In high-risk nmCRPC patients treated with apalutamide, enzalutamide or darolutamide at APCaRI affiliated cancer centres, median MFS, OS, PSA decline ≥ 50% from baseline (PSA50), and second progression free survival (PFS2) were calculated. Next generation gene sequencing (NGS) was performed on archival tumour tissue examining for genomic alterations in 500 genes, including homologous recombination repair (HRR), mismatch repair, tumour suppressor (TS), and PI3K/AKT oncogene (OG) groups. Analysis was conducted using Cox proportional hazards regression using wildtype cases as the reference group, while adjusting for PSA doubling time and presence of pelvic lymph nodes.

Results

Of 32 nmCRPC patients, 25 (78%) were treated with apalutamide, 5 (16%) with darolutamide and 2 (6%) with enzalutamide. 10 patients (31%) had TS/OG mutations (5 PTEN, 8 TP53, 2 PIK3CA), 3 (9%) had HRR gene mutations (2 ATM, 1 BRCA2) and 1 (3%) had 2 MLH1 mutations (microsatellite instability). All 5 patients who received subsequent therapy received abiraterone. Patients with TS/OG mutations had significantly shorter MFS (16.4 mo; HR 5.2; 95% CI 1.4 - 25.7; p = 0.018), PFS2 (22.1 mo; HR 15.4; 95% CI 1.9 - 126.3; p = 0.011) and OS (24.1 mo; HR 8.3; 95% CI 1.2 - 58.8; p = 0.035). Those with HRR mutations had significantly reduced PFS2 (median not reach [NR]; HR 40.4; 95% CI 1.6 - 1034.2; p = 0.025) and OS (NR; HR 21.7; 95% CI 1.1 - 446.1; p = 0.045). 3 (9%) patients did not achieve PSA50, including a patient with 2 MLH1 mutations.

Conclusions

This analysis demonstrates that nmCRPC patient with TS/OG and HRR gene mutations have poor clinical outcomes and may benefit from close follow-up. Our results underline the need for ongoing trials which examine novel targeted therapies (e.g. PARP Inhibitors, AKT inhibitors) in these molecularly defined nmCRPC subgroups.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

S. Yip.

Funding

Janssen Canada, Bayer Canada.

Disclosure

T.A. Bismar: Financial Interests, Institutional, Sponsor/Funding: Janssen Incorporated. S. Yip: Financial Interests, Institutional, Funding: Janssen Incorporated. All other authors have declared no conflicts of interest.

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