Germline BRCA1/2 mutation in metastatic PDAC (~5-7%): olaparib monotherapy maintenance af...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-HRD-STATUS-PDAC |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-PDAC |
| Sources | SRC-ESMO-PANCREATIC-2024 SRC-NCCN-PANCREATIC-2025 |
Actionability Facts
| Biomarker | BIO-HRD-STATUS |
|---|---|
| Variant | germline BRCA1/2 (gBRCAm) — primary FDA-actionable subset (~5-7% of pancreatic ductal adenocarcinoma); somatic BRCA / PALB2 with growing evidence |
| Disease | DIS-PDAC |
| ESCAT tier | IA |
| Recommended combinations | 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) |
| Evidence summary | 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). |
Notes
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.
Used By
No reverse references found in the YAML corpus.