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
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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