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.

Abstract

169 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.[Table: see text]

Prospective Study of Homologous Recombination Repair Gene Mutation Prevalence in Patients With Advanced Prostate Cancer From Latin America: Challenges and Future Approaches

“…Other efforts are being conducted in other populations that are not well represented in the published literature, such as the Russian population (ClinicalTrials.gov identifier: NCT04712890) or Indian population (Clinical Trials Registry India registration code: CTRI/2021/12/038578). 20…”

“…Other efforts are being conducted in other populations that are not well represented in the published literature, such as the Russian population (ClinicalTrials.gov identifier: NCT04712890) or Indian population (Clinical Trials Registry India registration code: CTRI/2021/12/038578). 20 Our PROSPECT cohort included a good representation from all seven participating countries with more than 15 patients per country included; notably, more patients were enrolled from Mexico (23%). Patients had overall a low tumor burden on the basis of the low frequency of visceral metastases and multiple organ involvement.…”

Prevalence of mutations in DNA repair genes in Russian patients with metastatic castration-resistant prostate cancer

“…Наиболее крупным многоцентровым проспективным исследованием в России является исследование ADAM, в которое включили 300 пациентов с диагнозом мКРРПЖ с последующим выполнением NGS (секвенирования нового поколения) [15].…”