Multicenter non-interventional study of prevalence of homologous recombination gene mutations and approaches to treatment of metastatic castration-resistant prostate cancer in Russia (ADAM)

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Abstract

Background. Prostate cancer (PCa) is one of the most common cancers of men. In 2022, 48,025 new PCa cases and 12,896 deaths from the disease were reported in Russia. Metastatic castration-resistant PCa still is one of the common causes of death in men.

Aim. To evaluate prevalence of homologous recombination repair gene (HRR) mutations in patients with metastatic castration-resistant PCa in Russia and to identify differences in clinical characteristics and treatment outcomes of patients with these mutations and without them.

Materials and methods. The study included 329 patients with metastatic castration-resistant PCa from 20 centers. Patients underwent molecular genetic analysis using next-generation sequencing to identify mutations in 14 HRR genes. The mutation status was determined in 3 routine laboratories and further validated in a central independent laboratory.

Results. The HRR gene mutations were detected in 59 (19.28 %) of 329 patients. The most common were ATM mutations – in 14 (4.57 %), BRCA2 – in 14 (4.57 %), BRCA1 – in 6 (1.96 %). All the patients received first-line therapy, with newgeneration antiandrogens and taxanes being used most frequently. The patients with HRR gene mutations had nearly

1.5 times lower median of progression-free survival (PFS) with first-line therapy: 12.8 months vs. 20.8 months in patients without mutations (p = 0.048). There was statistically significant difference in PFS between the observed groups with first-line therapy depending on the treatment group. In patients of general group having been treated with new-generation antiandrogen therapy, the median of PFS was 22 months, while in patients who had received taxanes it was 8.22 months (p <0.05). In patients with HRR gene mutations having been treated with first-line antiandrogenes of novel generation, the median of PFS was 20.5 months, while in patients without mutations the PFS median was 23.1 months (p = 0.14). In patients with mutations and having been treated with first-line taxanes, the PFS median was 6.15 months, while in patients without mutations it was 8.55 months (p = 0.4).

Conclusion. In our ADAM study in the Russian population, the proportion of carriers of the HRR gene mutations was slightly lower (19.28 %) than that reported in published randomized trials. There is also a different distribution structure and frequency of the most frequent mutations. Patients with the HRR gene mutations exhibited worse PFS rates and more aggressive course of the disease, which requires a special approach to treatment of this group of patients.

About the authors

B. Ya. Alekseev

N.A. Lopatkin Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center, Ministry of Health of Russia;
Medical Institute of Continuing Education, Russian Biotechnological University

ORCID iD: 0000-0002-3398-4128

Build. 1, 51 3rd Parkovaya St., Moscow 105425; 
11 Volokolamskoe Shosse, Moscow 125080

Russian Federation

Yu. V. Anzhiganova

A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncological Dispensary

ORCID iD: 0000-0002-8388-466X

16 1st Smolenskaya St., Krasnoyarsk 660133

Russian Federation

A. V. Sultanbaev

Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Bashkortostan

ORCID iD: 0000-0003-0996-5995

73/1 Oktyabrya Prospekt, Ufa 450054

Russian Federation

A. A. Bystrov

Moscow City Oncology Hospital No. 62, Moscow Healthcare Department

27 Istra, Moscow Region 143515

Russian Federation

A. S. Orlov

Sverdlovsk Regional Oncological Dispensary

ORCID iD: 0009-0002-2359-8351

29 Soboleva St., Yekaterinburg 620036

Russian Federation

G. V. Gopp

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

ORCID iD: 0000-0001-7674-694X

42 Blyukhera St., Chelyabinsk 454087

Russian Federation

A. V. Kopyltsov

Clinical Oncology Dispensary

ORCID iD: 0000-0003-3165-9118

9/1 Zavertyaeva St., Omsk 644013

Russian Federation

A. V. Lykov

Health Unit “Neftyanik”

ORCID iD: 0000-0002-1671-1195

12 Shiller St., Tyumen 625048

Russian Federation

V. A. Atduev

Privolzhsky District Medical Center, Federal Medical and Biological Agency

ORCID iD: 0000-0003-4478-7282

2 Nizhne-Volzhskaya Naberezhnaya, Nizhny Novgorod 603001

Russian Federation

G. N. Alekseeva

Primorsky Regional Oncological Dispensary

ORCID iD: 0000-0001-8253-2083

59 Russkaya St., Vladivostok 690105

Russian Federation

L. M. Rodygin

N.P. Napalkov Saint Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)

lit. A, 68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758

Russian Federation

S. A. Varlamov

Altai Regional Oncological Dispensary

110k Zmeinogorsky Trakt, Barnaul 656045

Russian Federation

A. V. Shestakov

Moscow Multidisciplinary Clinical Center “Kommunarka”, Moscow Healthcare Department

8 Sosenskiy Stan St., Kommunarka, Moscow 108814

Russian Federation

M. R. Maturov

Clinic of Bashkir State Medical University, Ministry of Health of Russia

ORCID iD: 0000-0002-2455-9058

2 Shafiyev St., Ufa 450083

Russian Federation

M. F. Urmantsev

Clinic of Bashkir State Medical University, Ministry of Health of Russia

ORCID iD: 0000-0002-4657-6625

2 Shafiyev St., Ufa 450083

Russian Federation

L. V. Lankina

A.S. Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department

Build. 1, 1 Novogireevskaya St., Moscow 111123

Russian Federation

E. L. Parsadanova

Sakhalin Regional Oncological Dispensary

ORCID iD: 0009-0001-5470-0219

3 Gorky St., Yuzhno-Sakhalinsk 693010

Russian Federation

V. Yu. Startsev

Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia

ORCID iD: 0000-0003-1243-743X

2 Litovskaya St., Saint Petersburg 194100

Russian Federation

O. V. Vedrova

AstraZeneca Pharmaceuticals LLC

Build. 1, 21 1st Krasnogvardeisky Proezd, Moscow 123112

Russian Federation

S. Yu. Andreev

AstraZeneca Pharmaceuticals LLC

Build. 1, 21 1st Krasnogvardeisky Proezd, Moscow 123112

Russian Federation

A. A. Perevoshchikov

AstraZeneca Pharmaceuticals LLC

Build. 1, 21 1st Krasnogvardeisky Proezd, Moscow 123112

Russian Federation

O. A. Mailyan

P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia

ORCID iD: 0000-0002-9787-8842

3 2nd Botkinskiy Proezd, Moscow 125284

Russian Federation

A. S. Kalpinskiy

P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia

Author for correspondence.
Email: dr.kalpinskiy@gmail.com
ORCID iD: 0000-0002-2209-3020

3 2nd Botkinskiy Proezd, Moscow 125284

Russian Federation

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