Germline BRCA1/2 mutação na PDAC metastática (~5-7%): olaparib manutenção em monoterapia af...
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| ID | BMA-HRD-STATUS-PDAC |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-PDAC |
| Fontes | SRC-ESMO-PANCREATIC-2024 SRC-NCCN-PANCREATIC-2025 |
Fatos de ação
| Biomarcador | BIO-HRD-STATUS |
|---|---|
| Variante | germline BRCA1/2 (gBRCAm) — subconjunto primário acionável da FDA (~5-7% de adenocarcinoma ductal pancreático); BRCA somática/PALB2 com evidência crescente |
| Doença | DIS-PDAC |
| Nível ESCAT | IA |
| Combinações recomendadas | FOLFIRINOX (or modified) 1L for fit gBRCAm PDAC (preferred per SRC-NCCN-PANCREATIC-2025, SRC-ESMO-PANCREATIC-2024), gemcitabine + cisplatin 1L (alternative platinum-based for non-FOLFIRINOX-eligible gBRCAm per SRC-NCCN-PANCREATIC-2025), olaparib monotherapy maintenance (post-platinum response gBRCAm per SRC-NCCN-PANCREATIC-2025, SRC-ESMO-PANCREATIC-2024) |
| Resumo das provas | Germline BRCA1/2 mutation in metastatic PDAC (~5-7%): olaparib monotherapy maintenance after ≥4 months of platinum-based 1L (FOLFIRINOX or gemcitabine/cisplatin) without progression is FDA-approved based on POLO (Golan NEJM 2019 — mPFS 7.4 vs 3.8 mo, HR 0.53; OS not significant) per SRC-NCCN-PANCREATIC-2025, SRC-ESMO-PANCREATIC-2024. Platinum-containing 1L is preferred for gBRCAm PDAC over gemcitabine + nab-paclitaxel because of platinum sensitivity (FOLFIRINOX response rates substantially higher in gBRCAm patients per multiple retrospective series cited in SRC-NCCN-PANCREATIC-2025). |
Notas
ESCAT IA / OncoKB Level 1 (gBRCAm). Somatic BRCA in PDAC has less evidence; PALB2 inclusion in NCCN PARP indication is conditional / Level 2A. Germline testing recommended for ALL pancreatic cancer at diagnosis per NCCN. POLO did not show OS benefit, but PFS improvement with low maintenance toxicity supports use. Source-gap: SRC-POLO-GOLAN-2019 not yet ingested.
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