Homologous-recombination-repair (HRR) gene alterations in metastatic castration-resistant...
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| ID | BMA-HRD-STATUS-PROSTATE |
|---|---|
| Type | Pertinence thérapeutique |
| État | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Maladies | DIS-PROSTATE |
| Sources | SRC-CIVIC SRC-EAU-PROSTATE-2024 SRC-ESMO-PROSTATE-2024 SRC-NCCN-PROSTATE-2025 |
Faits relatifs à l ' action en justice
| Biomarqueur | BIO-HRD-STATUS |
|---|---|
| Variante | HRR-pathway alteration — BRCA1/2 (~10% of mCRPC), ATM, CHEK2, PALB2, FANCA, RAD51 family, etc.; BRCA-mut subset is most actionable |
| Maladie | DIS-PROSTATE |
| Niveau ESCAT | IA |
| Combinaisons recommandées | olaparib monotherapy (HRR-mutated mCRPC 2L+ per SRC-NCCN-PROSTATE-2025, SRC-ESMO-PROSTATE-2024), olaparib + abiraterone + prednisone (BRCA-mutated 1L mCRPC per SRC-NCCN-PROSTATE-2025), niraparib + abiraterone + prednisone (BRCA-mutated 1L mCRPC per SRC-NCCN-PROSTATE-2025), talazoparib + enzalutamide (HRR-mutated 1L mCRPC per SRC-NCCN-PROSTATE-2025), rucaparib monotherapy (BRCA1/2 mCRPC per SRC-NCCN-PROSTATE-2025) |
| Résumé des faits | Homologous-recombination-repair (HRR) gene alterations in metastatic castration-resistant prostate cancer (mCRPC, ~25% somatic + germline): olaparib monotherapy is FDA-approved for BRCA1/2 (and several other HRR genes per FDA label) mCRPC after enzalutamide or abiraterone failure based on PROfound (de Bono NEJM 2020 — cohort A BRCA1/2/ATM mPFS 7.4 vs 3.6 mo, HR 0.34). Niraparib + abiraterone acetate (MAGNITUDE Chi JCO 2023) and olaparib + abiraterone (PROpel Clarke NEJM Evid 2022) are FDA-approved 1L combinations for HRR- altered mCRPC. Talazoparib + enzalutamide (TALAPRO-2 Agarwal Lancet 2023) is FDA-approved for HRR-mutated mCRPC 1L. Rucaparib has accelerated approval for BRCA1/2 mCRPC post-androgen-receptor- targeted therapy (TRITON3) per SRC-NCCN-PROSTATE-2025, SRC-ESMO-PROSTATE-2024, SRC-EAU-PROSTATE-2024. |
Notes
ESCAT IA / OncoKB Level 1 (BRCA1/2 strongest evidence; other HRR genes Level 1 by FDA label inclusion but heterogeneous evidence — ATM benefit weakest in PROfound subgroup analysis). EAU 2024 more conservative than NCCN on non-BRCA HRR PARP indications — documented position difference. Both germline and somatic testing recommended at metastatic diagnosis. Bibliographic records SRC-PROFOUND-DEBONO-2020 and SRC-TALAPRO2-AGARWAL-2023 are available; SRC-MAGNITUDE and SRC-PROPEL remain source gaps. Claim-level linkage requires clinical sign-off.
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