Treatment plan — Endometrial carcinoma

OpenOnco · DIS-ENDOMETRIAL · BIO-PIK3R1 (ESCAT IIB)

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OpenOnco · Treatment Plan

Treatment plan — Endometrial carcinoma

PLAN-BMA-PIK3R1_ENDOMETRIAL-V1 · v1 · 2026-08-17

Patient

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

DiagnosisEndometrial carcinoma

MOH / ICD-10C54

ICD-O-38380/3; C54.1

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
ESCAT: clinical review pendingBIO-PIK3R1	PIK3R1 activating/loss-of-function mutation — endometrial carcinoma; PI3K/AKT/mTOR pathway driver; co-occurs with PIK3CA in ~50% of EC	IIB	Standard care 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

Primary current-line option

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

Primary current-line option selected by ALGO-ENDOMETRIAL-ADVANCED-1L at step 1.

Other current-line alternatives (1 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

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

Current-line alternative 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

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

Patient with active or incompletely controlled pre-existing autoimmune or inflammatory disease (sarcoidosis, rheumatoid arthritis, IBD, SLE, autoimmune hepatitis, inflammatory myopathy, myasthenia gravis, or similar) is considered for immune checkpoint inhibitor (ICI) therapy — elevated risk of immune-related adverse events (irAE) flare or de-novo grade 3-4 irAE. Requires specialist (rheumatology / pulmonology / gastroenterology) pre-treatment review; prefer lower-irAE-burden backbone when options exist (pembrolizumab mono > ipilimumab+nivolumab).
Pre-existing autoimmune disease is present in ~10-15% of patients eligible for ICI therapy; historically excluded from pivotal trials. Real-world data (Abdel-Wahab 2018, 3557 pts) shows 55% experienced irAE flare and ~29% required…
RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISKSRC-SITC-ICI-IRAEMANAGEMENT-2021SRC-ESMO-ICI-TOXICITY-2022

CONTRA-AGGRESSIVE

Hard contraindications to escalation

—

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L)

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

Aggressive plan

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

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

MDT brief

Discussion questions (2, 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
OQ-BIOMARKER-DMMR-IHC
What is the status of Mismatch repair protein expression by IHC (BIO-DMMR-IHC)? It is required by track(s): IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO. Expected value: deficient.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ pathologist

MDT talk tree (3 steps)

#	Owner	Topic	Action
1	hematologist	Staging / disease burden	What is the current LDH? Marker of tumor burden and transformation.
2	pathologist	Biomarker status	What is the status of Mismatch repair protein expression by IHC (BIO-DMMR-IHC)? It is required by track(s): IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO. Expected value: deficient.
3	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Skills (recommended) — for consideration (1)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Data quality

Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.

Biomarker coverage: 0/1 known (0%), 1 missing, 0 default-track gaps
Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-CASCADE-LYNCH-FDR-POSITIVE, RF-CHRONIC-SEVERE-OBESITY-BMI40-PREVENTION, RF-CHRONIC-T2DM-CANCER-RISK-PREVENTION, RF-COWDEN-CONFIRMED-CARRIER, RF-COWDEN-FAMILY-HISTORY-SUSPICION, 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-IATROGENIC-COMBINED-HRT-PREVENTION, RF-IATROGENIC-TAMOXIFEN-ENDOMETRIAL-PREVENTION, RF-LIFESTYLE-OBESITY-CANCER-PREVENTION, RF-LIFESTYLE-SEDENTARY-PREVENTION, RF-LIFESTYLE-SUGARY-BEVERAGES-PREVENTION, RF-LYNCH-CONFIRMED-CARRIER, RF-LYNCH-FAMILY-HISTORY-SUSPICION, RF-POLE-POLD1-ENDOMETRIAL-LOW-RISK, RF-REPRODUCTIVE-BREAST-ENDOMETRIAL-PREVENTION, RF-REPRODUCTIVE-OCP-LONG-TERM, RF-REPRODUCTIVE-PCOS-ENDOMETRIAL-PREVENTION

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-DMMR-IHC`	Mismatch repair protein expression by IHC	pathologist	no	IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO	Verify result, method, specimen, and report date before sign-off. Expected/constraint: deficient

Technical MDT skill metadata (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	Sign-offs	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	0	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	0	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	0	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	0	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	0	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	0	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	0	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	0	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	0	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	0	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	0	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	0	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	0	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	0	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	0	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	0	cellular_therapy

Sources cited

SRC-ESMO-ENDOMETRIAL-2022: ESMO-ESGO-ESTRO Endometrial Consensus (2022)
SRC-GY018-MAKKER-2022: Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer ()
SRC-NCCN-UTERINE-2025: NCCN Uterine Neoplasms (2025.v2)
SRC-RUBY: Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer (2023)

Experimental options (clinical trials)

Last synced: 2026-08-17 · 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: 2026-08-17.

plan_id: PLAN-BMA-PIK3R1_ENDOMETRIAL-V1 | version: 1 | generated: 2026-08-17T08:06:32.082486+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.