TY - JOUR
T1 - The prevalence of gene mutations in homologous recombination repair pathways in Japanese patients with metastatic castration-resistant prostate cancer in real-world clinical practice
T2 - The multi-institutional observational ZENSHIN study
AU - Uemura, Hiroji
AU - Oya, Mototsugu
AU - Kamoto, Toshiyuki
AU - Sugimoto, Mikio
AU - Shinozaki, Kenta
AU - Morita, Kiyomi
AU - Koto, Ryo
AU - Takahashi, Mai
AU - Nii, Masahiro
AU - Shin, Eisei
AU - Nonomura, Norio
N1 - Funding Information:
We thank Catherine Rees of inScience Communications, Springer Healthcare, who provided writing and editorial assistance for the manuscript drafts. This medical writing assistance was funded by AstraZeneca K.K.
Funding Information:
This study was supported by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, who are codeveloping olaparib.
Publisher Copyright:
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - BRCA
KW - homologous recombination repair
KW - metastatic castration-resistance prostate cancer
KW - survival
UR - http://www.scopus.com/inward/record.url?scp=85141981476&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85141981476&partnerID=8YFLogxK
U2 - 10.1002/cam4.5333
DO - 10.1002/cam4.5333
M3 - Article
C2 - 36358026
AN - SCOPUS:85141981476
SN - 2045-7634
VL - 12
SP - 5265
EP - 5274
JO - Cancer Medicine
JF - Cancer Medicine
IS - 5
ER -
