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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

3825 - Prevalence of clinically actionable germline pathogenic variants (PVs) in advanced prostate cancer (aPC)

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Topics

Translational Research

Tumour Site

Prostate Cancer

Presenters

Andrew Hahn

Citation

Annals of Oncology (2018) 29 (suppl_8): viii271-viii302. 10.1093/annonc/mdy284

Authors

A.W. Hahn1, A.L. Kapron2, J. Boyle2, W. Kohlmann3, A. Poole1, D.M. Gill1, S. Greenberg3, P. Hale1, C. Teerlink2, B.L. Maughan1, L. Cannon-Albright2, N. Agarwal4, K.A. Cooney1

Author affiliations

  • 1 Medical Oncology, Huntsman Cancer Institute/University of Utah, 84112 - Salt Lake City/US
  • 2 Internal Medicine, University of Utah, 84112 - Salt Lake City/US
  • 3 Clinical Genetics, Huntsman Cancer Institute/University of Utah, 84112 - Salt Lake City/US
  • 4 Oncology/ Internal Medicine, Huntsman Cancer Institute, 84112 - Salt Lake City/US
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Resources

Abstract 3825

Background

Recently, germline PVs in 20 cancer predisposition genes were found in 11.8% of patients with aPC in a multi-center study (Pritchard et al, NEJM 2017).These PVs appeared to be predictive of response to PARP inhibitors (PARPi). We sought to evaluate the prevalence of clinically actionable PVs in a comparable aPC cohort and investigate possible associations of PVs with baseline patient and disease characteristics.

Methods

Clinical data and germline DNA samples from 352 consecutive aPC patients were retrospectively collected. A custom target panel (Qiagen QiaSeq V3) composed of 35 genes deemed clinically actionable and/or included in the Pritchard publication were sequenced on an Illumina HiSeq2500. GATK best practices were followed for alignment and variant calling. Variants were filtered based on ClinVar pathogenicity and reviewed by genetic counselors to confirm clinical significance. Baseline patient characteristics were compared using the Chi-squared, Fisher’s, and Mann-Whitney U tests.

Results

Clinically actionable, germline PVs were found in 26/352 (7.4%) of this aPC cohort. 11 of the 26 mutation carriers had a PV in BRCA1, BRCA2, or ATM (overall prevalence 3.1%). 96.6% of men were Caucasian of North European descent. Baseline characteristics were similar in those with or without PVs in clinically actionable genes, including age at diagnosis (p = 0.77), Gleason score (p = 0.22), or presence of metastatic disease at diagnosis (p = 0.08).

Conclusions

Our aPC cohort appears to have a lower prevalence of clinically actionable, germline PVs than previously reported studies. These findings may help inform recommendations for clinical genetic testing in this population, and help estimate the pace of enrollment on multiple ongoing clinical trials with PARPi in this population.

Clinical trial identification

Legal entity responsible for the study

Huntsman Cancer Institute and University of Utah.

Funding

Has not received any funding.

Editorial Acknowledgement

N/A

Disclosure

N. Agarwal: Consultancy: Pfizer, Novartis, Merck, Genentech, Eisai, Exelixis, Clovis, EMD Serono. All other authors have declared no conflicts of interest.

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