OpenOnco · Treatment Plan

Treatment plan — DIS-ENDOMETRIAL

PLAN-BMA-PIK3R1_ENDOMETRIAL-V1 · v1 · 2026-05-04

Patient

BMA-PIK3R1_ENDOMETRIAL · Algorithm: ALGO-ENDOMETRIAL-ADVANCED-1L

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
BIO-PIK3R1	PIK3R1 activating/loss-of-function mutation — endometrial carcinoma; PI3K/AKT/mTOR pathway driver; co-occurs with PIK3CA in ~50% of EC	IIB	SRC-NCCN-UTERINE-2025: Level Category 2A (Supports, Sensitivity/Response) SRC-ESGO-ENDOMETRIAL-2025: Level B (Supports, Sensitivity/Response)	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-specific companion diagnostic exists. ESCAT IIB: PI3K pathway activation in EC is targetable in principle; no PIK3R1-selected approved therapy.	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)	SRC-NCCN-UTERINE-2025 SRC-ESGO-ENDOMETRIAL-2025

Treatment options (2 tracks)

Standard plan

★ DEFAULT

Indication

IND-ENDOMETRIAL-ADVANCED-1L-PEMBRO-CHEMO

Regimen

Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L)

Drugs + NSZU

Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w · Continuous up to 2 years · IV ⚠ NSZU — not for this indication
Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
Paclitaxel (DRUG-PACLITAXEL) 175 mg/m² IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication

Reason

Engine default per algorithm ALGO-ENDOMETRIAL-ADVANCED-1L: {'step': 1, 'outcome': False, 'branch': {'result': 'IND-ENDOMETRIAL-ADVANCED-1L-PEMBRO-CHEMO'}, 'fired_red_flags': [], 'winner_red_flag': None}

Aggressive plan

Indication

IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO

Regimen

Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR)

Drugs + NSZU

Dostarlimab (DRUG-DOSTARLIMAB) 500 mg IV q3w → 1000 mg q6w maintenance · With chemo cycles 1-6 + maintenance up to 3 years · IV ✗ Not registered in UA
Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
Paclitaxel (DRUG-PACLITAXEL) 175 mg/m² IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication

Reason

Alternative track presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks

ID	Name	Priority	Category	Where to order	Needed for
TEST-CECT-CAP	CECT chest/abdomen/pelvis	Critical	imaging	—	all tracks
TEST-ER-PR-IHC	ER + PR immunohistochemistry on tumor	Critical	—	CSD Lab ✓ (code TBC)	all tracks

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Pembrolizumab + carbo + paclit

21-day cycles × Chemo x 6; pembro maintenance up to 2 years

Aggressive plan

Induction · Dostarlimab + carbo + paclitax

21-day cycles × Chemo x 6; dostarlimab maintenance up to 3 years

MDT brief

Skills (recommended) — for consideration (1)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 0 blocking)

OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist

Data quality

Unevaluated RedFlags: RF-ENDOMETRIAL-FIT-FOR-LENVATINIB-COMBO, RF-ENDOMETRIAL-FRAILTY-AGE, RF-ENDOMETRIAL-HIGH-RISK-BIOLOGY, RF-ENDOMETRIAL-INFECTION-SCREENING, RF-ENDOMETRIAL-ORGAN-DYSFUNCTION, RF-ENDOMETRIAL-TRANSFORMATION-PROGRESSION, RF-POLE-POLD1-ENDOMETRIAL-LOW-RISK

Skill catalog (1/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).

Specialist	skill_id	Version	Last reviewed	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-ESMO-ENDOMETRIAL-2022: ESMO-ESGO-ESTRO Endometrial Consensus (2022)
SRC-GY018-MAKKER-2022: (not in KB)
SRC-NCCN-UTERINE-2025: NCCN Uterine Neoplasms (2025.v2)
SRC-RUBY-MIRZA-2023: (not in KB)

Experimental options (clinical trials)

Last synced: 2026-05-04 · ctgov.

No active trials matched this scenario in ctgov.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).

Option	UA registration	NSZU	Cost orientation	Access pathway
Standard plan Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L) (REG-PEMBRO-CARBO-PACLI-ENDOM)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR) (REG-DOSTARLIMAB-CARBO-PACLI-ENDOM) 1/3 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.

plan_id: PLAN-BMA-PIK3R1_ENDOMETRIAL-V1 | version: 1 | generated: 2026-05-04T14:13:16.662930+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.