Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
VERIFIED-ENDOMETRIAL-L2-ENDOMETRIAL_2L_PEMBRO_LENVA_PM · Algorithm: ALGO-ENDOMETRIAL-2L
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 |
|---|
| No clinically actionable variants matched in this profile. |
Primary current-line option
- Indication
- IND-ENDOMETRIAL-2L-PEMBRO-LENVA-PMMR
- Regimen
- Pembrolizumab + Lenvatinib (KEYNOTE-775) — 2L pMMR endometrial
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w (alternatively 400 mg IV q6w) · IV until progression / unacceptable toxicity / max 35 cycles (~2 years) · IV ⚠ NSZU — not for this indication
- Lenvatinib (DRUG-LENVATINIB) 20 mg PO once daily continuous · Continuous PO daily · PO ⚠ NSZU — not for this indication
- Hard contraindications
- CI-PEMBROLIZUMAB-AUTOIMMUNE
- Reason
- Primary current-line option selected by ALGO-ENDOMETRIAL-2L at step 2.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-ENDOMETRIAL-2L-DOSTARLIMAB-DMMR
- Regimen
- Dostarlimab monotherapy (GARNET) — 2L+ dMMR endometrial
- Drugs + NSZU
- Dostarlimab (DRUG-DOSTARLIMAB) 500 mg IV q3w (cycles 1-4) then 1000 mg IV q6w (cycle 5+) · IV per protocol — until progression / unacceptable toxicity / max 2 years · IV ✗ Not registered in UA
- Hard contraindications
- CI-PEMBROLIZUMAB-AUTOIMMUNE
- 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-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CECT-CAP | CECT chest/abdomen/pelvis | Critical | imaging | — | all tracks |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-DMMR-IHC | MMR proteins IHC (MLH1 / MSH2 / MSH6 / PMS2) | Critical | histology | CSD Lab ✓ (code TBC) | all tracks |
| TEST-ECHO | Echocardiography | Standard | imaging | — | desired (standard) |
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 - Frailty profile precluding standard carbo+pacli ± pembro / dostarlimab in advanced/recurrent endometrial: ECOG ≥3, OR age ≥75 with ≥2 comorbidities, OR composite (age ≥70 + albumin <3.0 + Charlson ≥3), OR explicit "unfit for combination chemotherapy". Endometrial cancer median age at diagnosis is ~63 with rising incidence in elderly.
Frail elderly options: single-agent carboplatin (well tolerated, ORR 20-30%), weekly paclitaxel, or hormonal therapy (megestrol acetate / medroxyprogesterone) for ER/PR+ low-grade tumors. Pembrolizumab / dostarlimab monotherapy for…
RF-ENDOMETRIAL-FRAILTY-AGESRC-NCCN-UTERINE-2025SRC-ESMO-ENDOMETRIAL-2022 - Cardiac dysfunction (LVEF <50%) — limits anthracycline OR trastuzumab (HER2+ serous variant).
HER2+ serous endometrial subset eligible for trastuzumab + chemo.
RF-ENDOMETRIAL-ORGAN-DYSFUNCTIONSRC-NCCN-UTERINE-2025SRC-ESMO-ENDOMETRIAL-2022
CONTRA-AGGRESSIVE
Hard contraindications to escalation
- Pembrolizumab (and other PD-1/PD-L1 inhibitors) augment T-cell responses; in patients with active autoimmunity or post-transplant immunosuppression, this can precipitate severe organ-specific flares (colitis, hepatitis, pneumonitis, transplant rejection) that may be fatal or require transplant loss.
CI-PEMBROLIZUMAB-AUTOIMMUNE
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-ENDOMETRIAL-2L-PEMBRO-LENVA-PMMR)
- Do not prescribe without MMR/MSI testing — dMMR patients receive single-agent ICI preferentially.
- Do not ignore baseline + serial BP — Grade ≥3 hypertension in >30% of patients; antihypertensive prophylaxis from day 1.
- Do not forget to check proteinuria each cycle — lenvatinib VEGFR blockade.
- Do not prescribe in active autoimmune disease — irAE will progress uncontrollably.
- Do not continue at Grade ≥3 irAE without permanent discontinuation consideration.
- Do not combine with warfarin without INR monitoring — increased bleeding risk.
- Do not start lenvatinib ≤1 wk before or ≤2 wk after surgery — wound healing delay.
- Do not ignore Grade ≥3 diarrhea / hand-foot — dose-reduction mandatory (20→14→10→8 mg).
Aggressive plan (IND-ENDOMETRIAL-2L-DOSTARLIMAB-DMMR)
- Do not prescribe without confirmed dMMR / MSI-H status — efficacy in pMMR is limited.
- Do not prescribe in active autoimmune disease — irAE will progress uncontrollably.
- Do not continue at Grade ≥3 irAE without permanent discontinuation consideration.
- Do not use after prior ICI-exposure (RUBY/NRG-GY018 era 1L) — no data on reuse, consider pembro+lenva or chemo re-challenge.
- Do not forget Lynch syndrome screening (germline testing for MMR genes) for all dMMR patients — affects family + future tumor surveillance.
- Do not ignore ICI-pneumonitis at the onset of dyspnea — HRCT + corticosteroids.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Pembrolizumab + Lenvatinib (KEYNOTE-775) — 2L pMMR endometrial
21-day cycles × Pembrolizumab up to 35 cycles (~2 yr); lenvatinib until progression / intolerance
Aggressive plan
Induction · Dostarlimab monotherapy (GARNET) — 2L+ dMMR endometrial
21-day cycles × Until progression / unacceptable toxicity / max ~2 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-2L-DOSTARLIMAB-DMMR. Expected value: deficient (loss of MLH1/MSH2/MSH6/PMS2).
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-2L-DOSTARLIMAB-DMMR. Expected value: deficient (loss of MLH1/MSH2/MSH6/PMS2). |
| 3 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
Skills (recommended) — for consideration (1)
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-2L-DOSTARLIMAB-DMMR | Verify result, method, specimen, and report date before sign-off. Expected/constraint: deficient (loss of MLH1/MSH2/MSH6/PMS2) |
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-NCCN-UTERINE-2025: NCCN Uterine Neoplasms (2025.v2)
Experimental options (clinical trials)
Last synced: 2026-09-09 · 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 + Lenvatinib (KEYNOTE-775) — 2L pMMR endometrial (REG-PEMBRO-LENVATINIB-ENDOM) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Dostarlimab monotherapy (GARNET) — 2L+ dMMR endometrial (REG-DOSTARLIMAB-MONO-ENDOM) 1/1 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: 2026-09-09.