Patient
VERIFIED-GASTRIC-L2-GASTRIC_METASTATIC_2L_HER2_TDX · Algorithm: ALGO-GASTRIC-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 |
|---|
| BIO-HER2-SOLID | amplification / overexpression — IHC 3+ or (IHC 2+ + ISH amplified, HER2/CEP17 ≥2.0); ~15-20% of gastric/GEJ adenocarcinoma | IA | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Sensitivity/Response)
| HER2-positive gastric/GEJ adenocarcinoma (~15-20%): trastuzumab + chemotherapy is standard 1L (ToGA Bang Lancet 2010 — mOS 13.8 vs 11.1 mo, HR 0.74). Pembrolizumab + trastuzumab + chemo is FDA-approved 1L for HER2-positive PD-L1 CPS ≥1 metastatic gastric/GEJ disease per SRC-NCCN-GASTRIC-2025, SRC-ESMO-GASTRIC-2024 (KEYNOTE-811). Trastuzumab deruxtecan (T-DXd) is FDA-approved 2L+ for HER2-positive (IHC 3+ or 2+) advanced gastric/GEJ adenocarcinoma based on DESTINY-Gastric01 (Shitara NEJM 2020 — ORR 51% vs 14% with chemotherapy). | trastuzumab + fluoropyrimidine + platinum (1L per SRC-NCCN-GASTRIC-2025, SRC-ESMO-GASTRIC-2024)
pembrolizumab + trastuzumab + fluoropyrimidine + platinum (1L HER2+ PD-L1 CPS ≥1 per SRC-NCCN-GASTRIC-2025)
trastuzumab deruxtecan (2L+ post-trastuzumab progression per SRC-NCCN-GASTRIC-2025) | - SRC-NCCN-GASTRIC-2025
- SRC-ESMO-GASTRIC-2024
|
Primary current-line option
- Indication
- IND-GASTRIC-METASTATIC-2L-HER2-TDXD
- Regimen
- Trastuzumab deruxtecan (T-DXd) — 2L+ HER2+ gastric (DESTINY-Gastric01)
- Drugs + NSZU
- Trastuzumab deruxtecan (T-DXd) (DRUG-TRASTUZUMAB-DERUXTECAN) 6.4 mg/kg · IV q3 weeks until progression / unacceptable toxicity · IV ⚠ NSZU — not for this indication
- Reason
- Primary current-line option per algorithm ALGO-GASTRIC-2L: selected default was filtered; promoted first remaining current-line track
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-GASTRIC-METASTATIC-3L-TAS102
- Regimen
- Trifluridine-Tipiracil (TAGS) — 3L+ gastric/GEJ
- Drugs + NSZU
- Trifluridine + Tipiracil (DRUG-TRIFLURIDINE-TIPIRACIL) 35 mg/m² PO BID (based on FTD component) · Days 1-5 + 8-12 of each 28-day cycle (4 doses/week × 2 weeks, then 14-day rest) · PO ⚠ Out-of-pocket
- 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-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-CT-CHEST-ABDOMEN-PELVIS | CT chest + abdomen + pelvis with IV contrast | Critical | imaging | — | all tracks |
| TEST-ECHO | Echocardiography | Standard | imaging | — | aggressive |
| TEST-HER2-IHC-ISH-IF-RAS-WT | HER2 IHC + reflex ISH (gastric scoring criteria) | Standard | histology | CSD Lab ✓ (code TBC) | aggressive |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Fit performance status (ECOG 0-1): patient is fully active or restricted in physically strenuous activity but ambulatory and able to carry out light work. Eligible for full-dose chemotherapy and intensive regimens (CHOEP, BEACOPP-escalated, HD-MTX, ASCT consolidation, CAR-T).
Pan-disease eligibility gate. ECOG 0-1 is the canonical entry criterion for intensified regimens across DLBCL (CHOEP-21 in age ≤60 with elevated LDH per German High-Grade NHL Study Group), Hodgkin (BEACOPP-escalated), Burkitt…
RF-FITNESS-ECOG-FITSRC-NCCN-BCELL-2025SRC-ESMO-DLBCL-2024 - Frailty profile precluding standard FOLFOX+nivo / FLOT in gastric cancer: ECOG ≥3, OR (age ≥75 + Charlson ≥3), OR composite (age ≥70 + albumin <3.0 + ≥10% weight loss + sarcopenia — common in gastric cancer). Triggers regimen de-escalation (5-FU / capecitabine monotherapy, omit ICI/biologic).
Pre-treatment nutrition optimization (PEG/J-tube, parenteral nutrition bridge) often required. Nivolumab-containing regimens have lower symptomatic toxicity than FLOT for elderly — ATTRACTION-4 included ECOG 0-1 only; real-world frail…
RF-GASTRIC-FRAILTY-AGESRC-NCCN-GASTRIC-2025SRC-ESMO-GASTRIC-2024 - Treatment-defining biomarkers in metastatic gastric/GEJ adenocarcinoma: HER2+ (IHC 3+ OR 2+/ISH+) → trastuzumab+chemo TOGA / T-DXd 2L+; CLDN18.2+ (≥75% of tumor cells with 2+ membranous staining) → zolbetuximab+chemo SPOTLIGHT/GLOW; MSI-H → pembrolizumab mono; EBV+ subtype (TCGA molecular class) — distinct biology, ICI-favorable.
Sequential biomarker test cascade: HER2 IHC → ISH if 2+; PD-L1 CPS; MSI-H reflex; CLDN18.2 IHC. EBV by EBER-ISH if MSI-WT non-classic signet-ring. Multiple actionable biomarkers can co-exist (HER2+ MSI-H ~3% — ICI + trastuzumab…
RF-GASTRIC-HIGH-RISK-BIOLOGYSRC-NCCN-GASTRIC-2025SRC-ESMO-GASTRIC-2024
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-GASTRIC-METASTATIC-2L-HER2-TDXD)
- Do not ignore baseline + serial HRCT chest — ILD ~12% incidence, ~1% fatal.
- Do not continue at suspicion of pneumonitis — immediate hold + pulmonologist + corticosteroids.
- Do not use without HER2 reconfirmation on fresh biopsy when possible — HER2-loss after 1L is common.
- Do not prescribe at baseline LVEF <50% — cardiotoxicity of trastuzumab-based conjugates.
- Do not skip prophylactic high-emetogenic antiemetics — T-DXd HEC.
- Do not confirm the plan without verified funding pathway — NSZU 2026 does NOT cover T-DXd for stomach.
Standard plan (IND-GASTRIC-METASTATIC-3L-TAS102)
- Do not prescribe at ECOG ≥3 / rapidly declining PS — toxicity overcomes minimal benefit; consider best-supportive-care.
- Do not ignore CBC — neutropenia dose-limiting (~38%); G-CSF as needed.
- Do not forget renal-dose-adjustment at CrCl <60.
- Do not combine with other myelotoxic drugs without clear justification.
- Do not continue after the first progression — single-agent efficacy is limited; consider clinical-trial referral.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · Trastuzumab deruxtecan (T-DXd) — 2L+ HER2+ gastric (DESTINY-Gastric01)
21-day cycles × Until progression or unacceptable toxicity
Standard plan
Induction · Trifluridine-Tipiracil (TAGS) — 3L+ gastric/GEJ
28-day cycles × Until progression / unacceptable toxicity
MDT brief
Discussion questions (1, 0 blocking)
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 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| 3 | social_worker_case_manager | Specialist review | Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed. |
Skills (recommended) — for consideration (2)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Social worker / case manager recommended
Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.
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: 1/1 known (100%), 0 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-BREAST-CDH1-LOBULAR-CANDIDATE, RF-CASCADE-FAP-FDR-POSITIVE, RF-CASCADE-LYNCH-FDR-POSITIVE, RF-CHRONIC-ATROPHIC-GASTRITIS-PREVENTION, RF-CHRONIC-H-PYLORI-MALIGNANCY-PREVENTION, RF-CRONKHITE-CANADA-CONFIRMED, RF-FAP-CONFIRMED-CARRIER, RF-FAP-FAMILY-HISTORY-SUSPICION, RF-GASTRIC-CLDN18-2-ACTIONABLE, RF-GASTRIC-EMERGENCY-BLEED-OBSTRUCTION, RF-GASTRIC-FRAILTY-AGE, RF-GASTRIC-HIGH-RISK-BIOLOGY, RF-GASTRIC-INFECTION-SCREENING, RF-GASTRIC-PDL1-CPS-1-PLUS, RF-GASTRIC-TRANSFORMATION-PROGRESSION, RF-HDGC-CDH1-CONFIRMED-CARRIER, RF-IATROGENIC-LONG-TERM-PPI-GASTRIC-NET-PREVENTION, RF-JPS-CONFIRMED-CARRIER, RF-LIFESTYLE-SALTY-PICKLED-DIET-GASTRIC-PREVENTION, RF-LYNCH-CONFIRMED-CARRIER, RF-LYNCH-FAMILY-HISTORY-SUSPICION, RF-OLIGOMET-DEFINITION, RF-PEUTZ-JEGHERS-CONFIRMED-CARRIER, RF-PEUTZ-JEGHERS-FAMILY-HISTORY-SUSPICION
Technical MDT skill metadata (2/16 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-DESTINY-GASTRIC01-SHITARA-2020: Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer (2020)
- SRC-DESTINY-GASTRIC04-SHITARA-2025: Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer (2025)
- SRC-ESMO-GASTRIC-2024: ESMO Gastric Cancer (2024)
- SRC-NCCN-GASTRIC-2025: NCCN Gastric Cancer (v.3.2025)
Experimental options (clinical trials)
Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-07-15.
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|
| NCT06330064 | A Study To Evaluate The Efficacy And Safety Of Ifinatamab Deruxtecan (I-DXd) In Subjects With Recurrent Or Metastatic Solid Tumors (IDeate-PanTumor02) | PHASE2 | RECRUITING | — | Surrogate endpoint only | |
| NCT05059444 | ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation | N/A | RECRUITING | — | — | |
| NCT06364410 | Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors | PHASE1 | RECRUITING | — | Biomarker: enriched Phase 1 only Small N (<50) Single country | |
| NCT04389632 | A Study of Sigvotatug Vedotin in Advanced Solid Tumors | PHASE1 | RECRUITING | — | Biomarker: enriched Phase 1 only | |
Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.
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 |
|---|
| Aggressive plan Trastuzumab deruxtecan (T-DXd) — 2L+ HER2+ gastric (DESTINY-Gastric01) (REG-TDXD-GASTRIC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Trifluridine-Tipiracil (TAGS) — 3L+ gastric/GEJ (REG-TRIFLURIDINE-TIPIRACIL-GASTRIC) 1/1 component drug(s) not on NSZU formulary | ✓ registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Trial · NCT06330064 A Study To Evaluate The Efficacy And Safety Of Ifinatamab Deruxtecan (I-DXd) In Subjects With Recurrent Or Metastatic Solid Tumors (IDeate-PanTumor02) No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05059444 ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06364410 Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04389632 A Study of Sigvotatug Vedotin in Advanced Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-07-15.