Abstract 2643
Background
The BARCODE2 trial is investigating the response to platinum chemotherapy in men with advanced prostate cancer (PrCa) and a germline mutation in a DNA repair gene. We present the germline DNA sequencing results for 94 men who underwent genetic screening.
Methods
Eligible men with advanced PrCa consented to trial entry and provided a blood sample for DNA extraction and sequencing. All patients were known to have metastatic castration resistant PrCa (mCRPC) and had been treated with one or both of: Docetaxel chemotherapy and an androgen receptor targeted agent. Next generation sequencing (NGS) using a customised 115 gene panel (Agilent Technologies) was carried out on a MiSeq machine. Protein truncating variants (PTVs) in DNA repair genes by NGS were validated by Sanger sequencing. Patients found to carry a PTV were eligible to receive carboplatin upon disease progression.
Results
94 patients have undergone genetic testing. The median age of patients entering the trial was 67 (range 46-84). 21 patients (22%) carried one or more PTVs in a DNA repair gene: 3 carriers of a BRCA2 variant and 3 carriers of a variant in ALKBH3, 2 carriers of an ATM variant and 2 carriers of a PALB2 variant. One of the ATM variant carries also carried a PTV in POLQ and 2 further carriers of the same POLQ variant were identified. One carrier was identified to carry a variant in each of the following genes: MRE11A, PARP2, BLM, CHEK2, EXO1, LIG4, FANCD2, MSH5 and PMS1. Of the 20 identified PTVs, 11 are classified as pathogenic or likely pathogenic in ClinVar. There was no significant difference in the age at PrCa diagnosis between carriers and non-carriers (mean age 59 years vs 60; p = 0.34). There was also no difference in the presence of a family history of cancer.
Conclusions
The initial NGS results in the BARCODE2 trial demonstrate a higher frequency of germline mutations in mCRPC patients compared with previously published data. This study is ongoing and aims to sequence 450 patients. If the frequency of germline mutations in men with advanced PrCa is confirmed to be 20% or higher, this would support the roll-out of routine genetic testing in the oncology setting to identify men who may benefit from targeted treatments such as platinum chemotherapy and PARP inhibitors.
Clinical trial identification
NCT02955082.
Editorial acknowledgement
Legal entity responsible for the study
Institute of Cancer Research.
Funding
European Research Council.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5822 - Greek nursing students experience facing death in clinical practice
Presenter: Maria Dimoula
Session: Poster Display session 3
Resources:
Abstract
2866 - HOPEVOL: Hospice care appropriate to the wishes and needs of patients in the palliative terminal phase.
Presenter: Merel van Klinken
Session: Poster Display session 3
Resources:
Abstract
829 - Mindfulness-based stress reduction in early palliative care for advanced cancer patients : an italian single-centre study. MINDEEP
Presenter: Emilia Gianotti
Session: Poster Display session 3
Resources:
Abstract
2702 - Optimising Inpatient Oncology Care
Presenter: Lisa Judge
Session: Poster Display session 3
Resources:
Abstract
1527 - Analysis on the Implementation Results of Family Sickbed for Oncology Patients in Dongshi Township Health Centers from 2015 to 2017
Presenter: Yayu Huang
Session: Poster Display session 3
Resources:
Abstract
2054 - Exploring needs for palliative care and quality of life for oncology patients with advanced disease who undergo radiotherapy
Presenter: Foteini Antonopoulou
Session: Poster Display session 3
Resources:
Abstract
5605 - Cytotoxic contamination in cancer care settings – Risks and safety awareness among cancer nurses
Presenter: Sandra Lundman Vikberg
Session: Poster Display session 3
Resources:
Abstract
5769 - Understanding Chemotherapy - group education sessions prior to commencing chemotherapy
Presenter: Aileen McHale
Session: Poster Display session 3
Resources:
Abstract
2620 - Estimation of HPQ-based absenteeism and presenteeism in cancer patients via ResearchKit
Presenter: Shunsuke Kondo
Session: Poster Display session 3
Resources:
Abstract
4705 - Identifying falls-related variables and risk factors in hospitalised cancer patients
Presenter: Maria Montserrat Martí Dillet
Session: Poster Display session 3
Resources:
Abstract