ADAM: A multicenter, non-interventional, prospective cohort study for determination of prevalence of homologous recombination repair genes mutations (HRRm) in metastatic castrate-resistant prostate cancer (mCRPC)—Interim analysis.

Authors

null

Boris Alexeev

National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russian Federation

Boris Alexeev , Liudmila Lyubchenko , Marat Gordiev , Maxim Filipenko , Yulia Anzhiganova , Alexander Sultanbaev , Alexander Bystrov , Alexander Orlov , Galina Gopp , Evgeny Kopyltsov , Alexander Lykov , Vagif Atduev , Galina Alekseeva , Ovsep Mailyan , Vladislav Semenov , Olga Vedrova , Alexander Perevoschikov , Sergei Andreev , Logacheva Evgenia

Organizations

National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russian Federation, National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Moscow, Russian Federation, Molecular-Diagnostic Laboratory, National Bioservice, LLC, Saint Petersburg, Russian Federation, Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation, Krasnoyarsk Regional Clinical Oncological Dispensary Named After A.I. Kryzhanovsky, Krasnoyarsk, Russian Federation, Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Bashkortostan, Ufa, Russian Federation, Moscow City Oncological Hospital No. 62 of the Moscow City Health Department, Moscow, Russian Federation, State Autonomous Healthcare Institution of the Sverdlovsk Region "Sverdlovsk Regional Oncological Dispensary", Ekaterinburg, Russian Federation, State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine", Chelyabinsk, Russian Federation, Budgetary Healthcare Institution of the Omsk Region "Clinical Oncological Dispensary", Omsk, Russian Federation, Multidisciplinary Clinical Medical Center "Medical City", Tyumen, Russian Federation, Federal Budgetary Healthcare Institution "Volga District Medical Center" of the Federal Medical and Biological Agency, Nizhny Novgorod, Russian Federation, Primorsky Regional Oncological Dispensary, Vladivostok, Russian Federation, IM Sechenov First Moscow State Medical University, Moscow, Russian Federation, AstraZeneca, Moscow, Russian Federation

Research Funding

Pharmaceutical/Biotech Company

Background: The HRRm detection is used to prescribe PARP inhibitors in mCRPC patients. The frequency of HRR alterations has been investigated in several clinical studies, but the prevalence of HRRm in real clinical practice remains unclear. We conducted the first study to evaluate prevalence of HRRm in mCRPC patients in Russia. This interim analysis is aimed to provide HRRm rate in real practice in Russian population. Methods: Patients with mCRPC and available tumor tissue samples (FFPEs) were enrolled from October 2020 till May 2021. Samples were analyzed in 3 labs. Target enrichment using multiplex PCR and library preparation of genes involved in HRR (BRCA2, BRCA1, RAD54L, FANCL, BARD1, ATM, CHEK1, RAD51B, PALB2, RAD51D, CDK12, RAD51C, BRIP1, CHEK2) was performed using three different techniques: GeneReader NGS System (QIAGEN), KAPA HyperPlus and SeqCap EZ Choice (Roche) and in-house targeted NGS-panel. For last 2 sequencing was performed using MiSeq (Illumina). Results: In this interim analysis we included 331 mCRPC patients from 20 sites with median age 67 years, 86,7% caucasian. Family or personal history of oncological diseases had 66 (20%) of pts 300 FFPEs were analyzed by NGS, 31 (9%) were not valid (poor quality/not enough DNA). HRRm rate is 19,7% (59/300). Most frequently mutated genes ( > 1%) listed in the table below. Other mutations (RAD51B, RAD51C, BARD1, FANCL, RAD51D, RAD54L) were detected in 1-2 cases per gene. Conclusions: This first systematic analysis of HRRm in Russian population of mCRPC patients showed general consistency with previously reported HRRm data (19,7% in our trial in comparison with 27.9% in PROfound trial). Lab approach using different techniques in real practice has to be established.

Mutated gene
No. of cases
% from positive
% from all pts

(N = 300) positive+negative
BRCA2
14
24%
4,7%
ATM
13
22%
4,3%
BRCA1
7
12%
2,3%
CHEK2
6
10%
2,0%
CDK12
4
7%
1,3%
PALB2
4
7%
1,3%
BRIP1
3
5%
1,0%

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Abstract Details

Meeting

2022 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Prostate Cancer

Track

Prostate Cancer - Advanced,Prostate Cancer - Localized

Sub Track

Translational Research, Tumor Biology, Biomarkers, and Pathology

Citation

J Clin Oncol 40, 2022 (suppl 6; abstr 169)

DOI

10.1200/JCO.2022.40.6_suppl.169

Abstract #

169

Poster Bd #

J8

Abstract Disclosures