Cancer Medicine (Mar 2023)

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

  • Hiroji Uemura,
  • Mototsugu Oya,
  • Toshiyuki Kamoto,
  • Mikio Sugimoto,
  • Kenta Shinozaki,
  • Kiyomi Morita,
  • Ryo Koto,
  • Mai Takahashi,
  • Masahiro Nii,
  • Eisei Shin,
  • Norio Nonomura

DOI
https://doi.org/10.1002/cam4.5333
Journal volume & issue
Vol. 12, no. 5
pp. 5265 – 5274

Abstract

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Abstract 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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