HRR-altered mCSPC: evaluating talazoparib + enzalutamide + ADT

Authored by Natalia Gandur, published on 2026-06-23 22:06:00.0

  1. Confirm HRR-altered mCSPC treatment context
    • 1. Confirm mCSPC
      Metastatic castration-sensitive prostate cancer
      • 2. Start / continue ADT
        Androgen deprivation therapy
        • 3. Obtain HRR testing
          Germline and/or somatic testing for homologous recombination repair (HRR) alterations
          • 4. HRR alteration present?
            • Yes
              • 5. Assess suitability for talazoparib + enzalutamide + ADT
                Performance status / functional status; Hematologic reserve (CBC, anemia, platelet count); Comorbidities and organ function (hepatic, renal); CNS history / seizure risk; Drug interactions and concomitant medications; Access / regulatory status / reimbursement; Ability to adhere and undergo monitoring
                • 6. Eligible and feasible?
                  • Yes
                    • Consider TALAPRO-3–based strategy: talazoparib + enzalutamide + ADT
                      For HRR-altered mCSPC where supported by trial data, approval/access, and expert consensus
                      • 7. Monitor during therapy
                        CBC (anemia, neutropenia, thrombocytopenia); Fatigue, nausea, other AEs; Blood pressure, falls risk; PSA and imaging response; Adherence and quality of life
                        • 8. At progression
                          Reassess disease state → Consider next-line therapy, clinical trials, and supportive care
                  • No
                    • Use standard ARPI-based mCSPC pathway
                      Or other appropriate intensification strategy based on patient, disease, and access factors
                      • 7. Monitor during therapy
                        CBC (anemia, neutropenia, thrombocytopenia); Fatigue, nausea, other AEs; Blood pressure, falls risk; PSA and imaging response; Adherence and quality of life
                        • 8. At progression
                          Reassess disease state → Consider next-line therapy, clinical trials, and supportive care
            • No / Unknown
              • Follow standard mCSPC treatment pathway
                Use guideline-recommended ARPI-based or other standard intensification strategies
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