HRR-altered first-line mCRPC: where talazoparib + enzalutamide fits

Authored by Natalia Gandur, published on 2026-06-23 22:51:32.0

  1. 1. Confirm mCRPC
    Metastatic castration-resistant prostate cancer
    • 2. Continue ADT / castration backbone
      GnRH analogue or prior bilateral orchiectomy
      • 3. First-line mCRPC setting
        No prior systemic therapy for mCRPC
        • 4. Obtain HRR testing
          Tissue or ctDNA-based testing for HRR gene alterations
          • 5. HRR alteration present?
            • No / Unknown
              • Follow standard mCRPC treatment pathway
            • Yes
              • 6. Assess suitability for enzalutamide + talazoparib
                • Performance status • Prior ARPI exposure • CBC / marrow reserve • Renal function • Drug interactions • Access / monitoring feasibility
                • 7. Eligible / feasible?
                  • Yes
                    • Talazoparib + enzalutamide + ongoing ADT
                      • 9. At progression
                        Reassess post-PARP / post-ARPI sequencing, chemotherapy, radioligand therapy, clinical trial options, and supportive care
                        • HRR-mutated mCRPC only: confirm biomarker, safety, access, and monitoring.
                          Confirm biomarker status, access, marrow reserve, and monitoring capacity.
                  • No
                    • Use alternative standard mCRPC pathway
                      • 9. At progression
                        Reassess post-PARP / post-ARPI sequencing, chemotherapy, radioligand therapy, clinical trial options, and supportive care
                        • HRR-mutated mCRPC only: confirm biomarker, safety, access, and monitoring.
                          Confirm biomarker status, access, marrow reserve, and monitoring capacity.
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