Opinion

Video

BRCA Mutations in mHSPC: Impact on Therapy Selection

Paul E. Dato, MD, discusses how the presence of a BRCA mutation can influence treatment selection and sequencing, supporting consideration of upfront triplet therapy intensification and planning for earlier integration of PARP inhibitors when castration resistance develops.

Clinical Brief: Genetic Considerations in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Main Discussion Topics

  • Implications of BRCA Mutations: More aggressive molecular phenotype requiring consideration of treatment intensification
  • Genetic Counseling: Recommended for all BRCA-positive patients due to implications for family members and risk of second malignancies
  • Treatment Strategy Modification: Support for triplet therapy with androgen deprivation therapy, chemotherapy, and androgen receptor targeting agent
  • Future Therapy Planning: Early integration of PARP inhibitors when castration resistance develops

Key Points for Physicians

  • Multiple clinical trials support PARP inhibitor use in castration-resistant disease with HRR mutations:
    • TALAPRO trial (talazoparib with enzalutamide)
    • PROpel trial (olaparib with abiraterone)
    • MAGNITUDE trial (niraparib with abiraterone)
    • PROfound trial (olaparib as single agent)
    • TRITON trial (rucaparib as single agent)
  • Trial data should influence initial androgen receptor–targeted agent selection
  • PARP inhibitors not currently indicated for hormone-sensitive disease

Notable Insights

The presence of HRR mutations warrants consideration of more aggressive upfront treatment approaches, even in borderline high-volume disease, and planning for earlier integration of PARP inhibitors upon disease progression.

Clinical Significance

Genetic testing results significantly influence both immediate treatment decisions and long-term therapeutic planning in metastatic prostate cancer management, underscoring the importance of precision medicine approaches.

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