PIK3R1-Mutationen treten in ~33% des Endometriumkarzinoms (EC) auf — unter den höchsten...
Deterministische Ansicht der Quelle YAML Entität. Klinische Autorität bleibt mit den zitierten Quell-IDs und Rezensenten Sign-off Zustand.
| ID | BMA-PIK3R1-ENDOMETRIAL |
|---|---|
| Art | Therapeutische Relevanz |
| Status | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Erkrankungen | DIS-ENDOMETRIAL |
| Quellen | SRC-ESGO-ENDOMETRIAL-2025 SRC-NCCN-UTERINE-2025 |
Fakten zur Handlungsfähigkeit
| Biomarker | BIO-PIK3R1 |
|---|---|
| Variante | PIK3R1 activating/loss-of-function mutation — endometrial carcinoma; PI3K/AKT/mTOR pathway driver; co-occurs with PIK3CA in ~50% of EC |
| Erkrankung | DIS-ENDOMETRIAL |
| ESCAT-Stufe | IIB |
| Empfohlene Kombinationen | lenvatinib 20 mg PO QD + pembrolizumab 200 mg IV q3w — FDA-approved for pMMR/MSS advanced EC (KEYNOTE-775); not PIK3R1-specific but active in PI3K-pathway-altered EC, everolimus 10 mg PO QD + letrozole 2.5 mg PO QD — off-label for hormone-receptor-positive, pMMR advanced EC (GOG-0248 data; ~32% CBR), alpelisib 300 mg PO QD + fulvestrant — investigational for PIK3CA/PIK3R1-mutant HR+ EC (basket trial regimen; not FDA-approved for EC) |
| Zusammenfassung der Beweise | PIK3R1 mutations occur in ~33% of endometrial carcinoma (EC) — among the highest frequencies in any cancer. PIK3R1 mutations activate PI3K/AKT/mTOR signaling by reducing p85α inhibitory constraint on the p110α catalytic subunit. PI3K pathway activation is present in ~50% of EC (PIK3CA + PIK3R1 + PTEN combined). Therapeutic evidence for PI3K/mTOR pathway inhibitors in EC: Lenvatinib + pembrolizumab (KEYNOTE-775, FDA 2021): approved for advanced/recurrent mismatch repair proficient (pMMR/MSS) EC after prior chemotherapy — not specifically PIK3R1-selected; lenvatinib inhibits multiple RTKs including VEGFR/FGFR rather than PI3K. Everolimus + letrozole (GOG-0248): showed activity in recurrent EC (~32% CBR) but is not FDA-approved for EC; used off-label in hormone-receptor-positive EC. Alpelisib (PI3Kα inhibitor, FDA-approved for PIK3CA-mutant HR+ breast cancer): not approved for EC but under investigation in PI3K-pathway-altered EC (MATCH subprotocol trials, SUMMIT basket trial). PIK3R1 mutations may sensitize to alpelisib via the same PI3Kα activation mechanism as PIK3CA. No PIK3R1-spec... |
Anmerkungen
ESCAT IIB: PIK3R1 mutation in EC activates the same PI3K/AKT/mTOR pathway as PIK3CA and PTEN loss, but currently lacks a PIK3R1-specific companion diagnostic and approved targeted therapy. Management: (1) First, characterize EC molecular class (POLE, MMR, p53, CTNNB1) to guide first-line adjuvant decisions; (2) PIK3R1 testing is relevant for trial eligibility (PI3K pathway basket trials), not for current standard therapy selection; (3) For recurrent/advanced pMMR EC, lenvatinib + pembrolizumab is standard regardless of PIK3R1 status (KEYNOTE-775); (4) Alpelisib access: compassionate use or clinical trial for PIK3R1-mutant EC; (5) PTEN IHC (surrogate for PTEN loss, co-occurring with PIK3R1 in many EC) provides complementary PI3K pathway information.
Verwendet von
Keine Rückverweise im YAML-Korpus gefunden.