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The prevalence of gene mutations in homologous recombination repair pathways in Japanese patients with metastatic castration‐resistant prostate cancer in real‐world clinical practice: The multi‐institutional observational ZENSHIN study

BACKGROUND: Metastatic castration‐resistant prostate cancer (mCRPC) is a genetically heterogeneous disease with a poor prognosis. The prevalence of mutations in homologous recombination repair (HRR) pathway genes, including BRCA1/2, as well as treatment patterns and clinical outcomes, are not well c...

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Autores principales: Uemura, Hiroji, Oya, Mototsugu, Kamoto, Toshiyuki, Sugimoto, Mikio, Shinozaki, Kenta, Morita, Kiyomi, Koto, Ryo, Takahashi, Mai, Nii, Masahiro, Shin, Eisei, Nonomura, Norio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10028105/
https://www.ncbi.nlm.nih.gov/pubmed/36358026
http://dx.doi.org/10.1002/cam4.5333
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author Uemura, Hiroji
Oya, Mototsugu
Kamoto, Toshiyuki
Sugimoto, Mikio
Shinozaki, Kenta
Morita, Kiyomi
Koto, Ryo
Takahashi, Mai
Nii, Masahiro
Shin, Eisei
Nonomura, Norio
author_facet Uemura, Hiroji
Oya, Mototsugu
Kamoto, Toshiyuki
Sugimoto, Mikio
Shinozaki, Kenta
Morita, Kiyomi
Koto, Ryo
Takahashi, Mai
Nii, Masahiro
Shin, Eisei
Nonomura, Norio
author_sort Uemura, Hiroji
collection PubMed
description BACKGROUND: Metastatic castration‐resistant prostate cancer (mCRPC) is a genetically heterogeneous disease with a poor prognosis. The prevalence of mutations in homologous recombination repair (HRR) pathway genes, including BRCA1/2, as well as treatment patterns and clinical outcomes, are not well characterized among Japanese men with mCRPC. METHODS: This multicenter, noninterventional cohort study enrolled Japanese men with mCRPC from 24 institutions between 2014 and 2018. Mutations in the 15 HRR‐related genes were assessed using archival primary or metastatic tumor samples. Patterns of sequential therapies for mCRPC were investigated. Patients were followed up for survival evaluation including prostate‐specific antigen progression‐free survival (PSA‐PFS) and overall survival (OS). RESULTS: Of the 143 patients analyzed, HRR‐related mutations were detected in 51 patients (35.7%). The most frequently mutated genes were CDK12 (N = 19, 13.3%), followed by BRCA2 (N = 18, 12.6%), ATM (N = 8, 5.6%), and CHEK2 (N = 3, 2.1%). The most common type of first‐line therapy for mCRPC was next‐generation hormonal agents (NHA, 44.4%), followed by first‐generation antiandrogens (FGA, 30.3%), and taxanes (22.5%). Commonly prescribed first−/second‐line sequential regimens included FGA/NHA (17.6%), NHA/NHA (15.5%), and NHA/taxanes (14.1%). The median PSA‐PFS and OS for the entire cohort were 5.6 and 26.1 months, respectively. Patients carrying BRCA1/2 mutations had numerically shorter PSA‐PFS (median 3.3 vs. 5.9 months) and OS (median 20.7 vs. 27.3 months) than those without mutations. CONCLUSIONS: In conclusion, approximately one‐third of Japanese patients with mCRPC carried mutations in HRR‐related genes in this study. The real‐world outcomes of mCRPC are poor with conventional therapy, warranting an expansion of treatment options based on genetic abnormalities of the disease.
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spelling pubmed-100281052023-03-22 The prevalence of gene mutations in homologous recombination repair pathways in Japanese patients with metastatic castration‐resistant prostate cancer in real‐world clinical practice: The multi‐institutional observational ZENSHIN study Uemura, Hiroji Oya, Mototsugu Kamoto, Toshiyuki Sugimoto, Mikio Shinozaki, Kenta Morita, Kiyomi Koto, Ryo Takahashi, Mai Nii, Masahiro Shin, Eisei Nonomura, Norio Cancer Med RESEARCH ARTICLES BACKGROUND: Metastatic castration‐resistant prostate cancer (mCRPC) is a genetically heterogeneous disease with a poor prognosis. The prevalence of mutations in homologous recombination repair (HRR) pathway genes, including BRCA1/2, as well as treatment patterns and clinical outcomes, are not well characterized among Japanese men with mCRPC. METHODS: This multicenter, noninterventional cohort study enrolled Japanese men with mCRPC from 24 institutions between 2014 and 2018. Mutations in the 15 HRR‐related genes were assessed using archival primary or metastatic tumor samples. Patterns of sequential therapies for mCRPC were investigated. Patients were followed up for survival evaluation including prostate‐specific antigen progression‐free survival (PSA‐PFS) and overall survival (OS). RESULTS: Of the 143 patients analyzed, HRR‐related mutations were detected in 51 patients (35.7%). The most frequently mutated genes were CDK12 (N = 19, 13.3%), followed by BRCA2 (N = 18, 12.6%), ATM (N = 8, 5.6%), and CHEK2 (N = 3, 2.1%). The most common type of first‐line therapy for mCRPC was next‐generation hormonal agents (NHA, 44.4%), followed by first‐generation antiandrogens (FGA, 30.3%), and taxanes (22.5%). Commonly prescribed first−/second‐line sequential regimens included FGA/NHA (17.6%), NHA/NHA (15.5%), and NHA/taxanes (14.1%). The median PSA‐PFS and OS for the entire cohort were 5.6 and 26.1 months, respectively. Patients carrying BRCA1/2 mutations had numerically shorter PSA‐PFS (median 3.3 vs. 5.9 months) and OS (median 20.7 vs. 27.3 months) than those without mutations. CONCLUSIONS: In conclusion, approximately one‐third of Japanese patients with mCRPC carried mutations in HRR‐related genes in this study. The real‐world outcomes of mCRPC are poor with conventional therapy, warranting an expansion of treatment options based on genetic abnormalities of the disease. John Wiley and Sons Inc. 2022-11-10 /pmc/articles/PMC10028105/ /pubmed/36358026 http://dx.doi.org/10.1002/cam4.5333 Text en © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle RESEARCH ARTICLES
Uemura, Hiroji
Oya, Mototsugu
Kamoto, Toshiyuki
Sugimoto, Mikio
Shinozaki, Kenta
Morita, Kiyomi
Koto, Ryo
Takahashi, Mai
Nii, Masahiro
Shin, Eisei
Nonomura, Norio
The prevalence of gene mutations in homologous recombination repair pathways in Japanese patients with metastatic castration‐resistant prostate cancer in real‐world clinical practice: The multi‐institutional observational ZENSHIN study
title The prevalence of gene mutations in homologous recombination repair pathways in Japanese patients with metastatic castration‐resistant prostate cancer in real‐world clinical practice: The multi‐institutional observational ZENSHIN study
title_full The prevalence of gene mutations in homologous recombination repair pathways in Japanese patients with metastatic castration‐resistant prostate cancer in real‐world clinical practice: The multi‐institutional observational ZENSHIN study
title_fullStr The prevalence of gene mutations in homologous recombination repair pathways in Japanese patients with metastatic castration‐resistant prostate cancer in real‐world clinical practice: The multi‐institutional observational ZENSHIN study
title_full_unstemmed The prevalence of gene mutations in homologous recombination repair pathways in Japanese patients with metastatic castration‐resistant prostate cancer in real‐world clinical practice: The multi‐institutional observational ZENSHIN study
title_short The prevalence of gene mutations in homologous recombination repair pathways in Japanese patients with metastatic castration‐resistant prostate cancer in real‐world clinical practice: The multi‐institutional observational ZENSHIN study
title_sort prevalence of gene mutations in homologous recombination repair pathways in japanese patients with metastatic castration‐resistant prostate cancer in real‐world clinical practice: the multi‐institutional observational zenshin study
topic RESEARCH ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10028105/
https://www.ncbi.nlm.nih.gov/pubmed/36358026
http://dx.doi.org/10.1002/cam4.5333
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