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
4596 - A Phase 2, Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-Mutant Melanoma Brain Metastasis (MBM) (POLARIS)
Presenter: Michael Davies
Session: Poster Display session 3
Resources:
Abstract
1891 - Continuation of annual screening mammograms and breast-cancer mortality in women over 70
Presenter: Xabier Garcia De Albeniz
Session: Poster Display session 3
Resources:
Abstract
5587 - Introducing standardized medical procedure and dynamic decision support program in precision oncology for the community of practice
Presenter: Istvan Petak
Session: Poster Display session 3
Resources:
Abstract
4757 - Effectively using primary care givers in oncology care through capacity building, task sharing and techno-mentoring.
Presenter: Dinesh Pendharkar
Session: Poster Display session 3
Resources:
Abstract
4497 - A single institution review of capecitabine related acute admissions and cost analysis
Presenter: Gemma Dart
Session: Poster Display session 3
Resources:
Abstract
2187 - Health status of middle-aged and older cancer survivors in China: results from the China Health and Retirement Longitudinal Study (CHARLS)
Presenter: Jiarui Li
Session: Poster Display session 3
Resources:
Abstract
5101 - Crossed looks on lung cancer perception and knowledge from general public and physicians in France: results of a two-fold survey
Presenter: Céline Mascaux
Session: Poster Display session 3
Resources:
Abstract
4354 - Knowledge and perception of clinical trials (CTs) and attitude towards participation among Polish oncological patients - A pilot survey
Presenter: Artur Kotowski
Session: Poster Display session 3
Resources:
Abstract
3499 - Achieving best possible cancer treatment outcomes in care pathways through benchmarking; ABC-Benchmarking
Presenter: Anke Wind
Session: Poster Display session 3
Resources:
Abstract
2270 - Impact of 10-day Fulbright Specialist Program (FSP) and Project Pink Blue (PPB) Education Sessions on Medical Oncology knowledge among Doctors that treat cancer in Nigeria
Presenter: Mike Martin
Session: Poster Display session 3
Resources:
Abstract