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
3047 - Health-related quality of life in Greek haematogical malignancies patients undergoing chemotherapy
Presenter: Maria Lavdaniti
Session: Poster Display session 3
Resources:
Abstract
1121 - Experiences of endocrine therapy after breast cancer surgery
Presenter: Susanne Ahlstedt Karlsson
Session: Poster Display session 3
Resources:
Abstract
2305 - The effects of progressive muscle relaxation and mindfulness meditation on fatigue, coping styles, and quality of life in breast cancer patients receiving adjuvant paclitaxel regimen: An-assessor blinded, three-arm randomized controlled trial
Presenter: Zehra Gok Metin
Session: Poster Display session 3
Resources:
Abstract
4561 - Agreement between breast cancer patients and oncologists on the severity of patients’ symptoms and functions during a one-year follow-up after treatment.
Presenter: Randi Reidunsdatter
Session: Poster Display session 3
Resources:
Abstract
1768 - Taste Changes and Associated Factors in Patients Receiving Chemotherapy
Presenter: Gulcan Bagcivan
Session: Poster Display session 3
Resources:
Abstract
1830 - CART-19: a comparative between literature versus experience
Presenter: Cassandra Andersson Vila
Session: Poster Display session 3
Resources:
Abstract
4027 - Unplanned emergency department use by people receiving ambulatory anti-cancer agents with potential febrile neutropenia
Presenter: Meritxell Casanovas-Blanco
Session: Poster Display session 3
Resources:
Abstract
4754 - Examining the benefits of medical exercise during radiotherapy in patients after mastectomy
Presenter: Nikolina Dodlek
Session: Poster Display session 3
Resources:
Abstract
2510 - Assessment Quality of Life with Hand-Foot Syndrome Induced by Apatinib Combined with Anti-PD-1 Therapy in NSCLC
Presenter: Qi Jiang
Session: Poster Display session 3
Resources:
Abstract
2989 - Adverse effects of chemotherapy influence the patients’ quality of life : Analysis of implicated factors
Presenter: Maria Lavdaniti
Session: Poster Display session 3
Resources:
Abstract