Patient
VERIFIED-CRC-L2-CRC_METASTATIC_2L_HER2_AMP_TUC · Algorithm: ALGO-CRC-METASTATIC-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); ~3-5% of metastatic colorectal cancer (RAS/BRAF-WT) | IB | Molecular evidence option - SRC-CIVIC: Level B (Supports, Sensitivity/Response)
Resistance or avoidance signal Trial or research option - SRC-CIVIC: Level D (Supports, Sensitivity/Response)
| HER2-amplified metastatic colorectal cancer (~3-5% in RAS/BRAF-WT population): tucatinib + trastuzumab is FDA-approved 2L+ for HER2- positive RAS-WT mCRC based on MOUNTAINEER (Strickler Lancet Oncol 2023 — ORR 38%, mDOR 12 mo) per SRC-NCCN-COLON-2025. Trastuzumab deruxtecan also has activity (DESTINY-CRC01 Siena Lancet Oncol 2021 — ORR 45% in HER2 IHC 3+ RAS-WT) and tumor-agnostic FDA approval (2024) for HER2-positive solid tumors that have progressed on prior therapy. Older trastuzumab + lapatinib (HERACLES) is referenced as alternative. RAS-mutant tumors should not receive HER2-directed therapy in 2L because RAS-driven resistance is well-documented per SRC-NCCN-COLON-2025. | tucatinib + trastuzumab (2L+ HER2+ RAS-WT mCRC per SRC-NCCN-COLON-2025)
trastuzumab deruxtecan (2L+ HER2+ mCRC per SRC-NCCN-COLON-2025)
trastuzumab + lapatinib (alternative per HERACLES, listed in SRC-NCCN-COLON-2025) | - SRC-NCCN-COLON-2025
- SRC-ESMO-COLON-2024
|
Primary current-line option
- Indication
- IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB
- Regimen
- Tucatinib + Trastuzumab (MOUNTAINEER, HER2+ RAS-WT mCRC)
- Drugs + NSZU
- Tucatinib (DRUG-TUCATINIB) 300 mg PO BID continuous · Continuous · PO ✗ Not registered in UA
- Trastuzumab (DRUG-TRASTUZUMAB) 8 mg/kg IV loading then 6 mg/kg IV q3w · IV q3w · IV ⚠ NSZU — not for this indication
- Reason
- Primary current-line option selected by ALGO-CRC-METASTATIC-2L at step 4; branch-driving red flag: RF-CRC-HER2-AMP-ACTIONABLE.
Other current-line alternatives (7 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-CRC-METASTATIC-2L-MSI-H-PEMBRO
- Regimen
- Pembrolizumab monotherapy (MSI-H mCRC 1L)
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w OR 400 mg IV q6w · Until progression / unacceptable toxicity / 35 cycles (about 2 years) · IV ⚠ NSZU — not for this indication
- Hard contraindications
- CI-PEMBROLIZUMAB-AUTOIMMUNE
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-2L-BRAF-BEACON
- Regimen
- Encorafenib + Cetuximab (BEACON CRC)
- Drugs + NSZU
- Encorafenib (DRUG-ENCORAFENIB) 300 mg PO daily continuous · Continuous · PO ⚠ Out-of-pocket
- Cetuximab (DRUG-CETUXIMAB) 400 mg/m² IV loading then 250 mg/m² weekly · IV weekly · IV ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-2L-KRAS-G12C-SOTORASIB-CETUXIMAB
- Regimen
- Sotorasib + Cetuximab (CodeBreaK 300, KRAS G12C+ mCRC)
- Drugs + NSZU
- Sotorasib (DRUG-SOTORASIB) 960 mg PO once daily continuous · Continuous · PO ✗ Not registered in UA
- Cetuximab (DRUG-CETUXIMAB) 500 mg/m² IV q2w (preferred) OR 400 mg/m² loading then 250 mg/m² weekly · IV q2w · IV ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-2L-HER2-AMP-T-DXD
- Regimen
- Trastuzumab-deruxtecan monotherapy (DESTINY-CRC01, HER2+ mCRC)
- Drugs + NSZU
- Trastuzumab deruxtecan (T-DXd) (DRUG-TRASTUZUMAB-DERUXTECAN) 6.4 mg/kg IV q3w · IV q3w (DESTINY-CRC01 dosing; lower than 5.4 mg/kg breast/gastric dose for ILD risk balance) · IV ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-2L-EGFRI-RECHALLENGE
- Regimen
- FOLFOX + Cetuximab
- Drugs + NSZU
- Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV day 1 · IV ✓ NSZU covered
- Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 · IV ✓ NSZU covered
- 5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus + 2400 mg/m² CIV over 46h · Day 1 bolus, day 1-2 CIV · IV ✓ NSZU covered
- Cetuximab (DRUG-CETUXIMAB) 500 mg/m² q2w (preferred for FOLFOX schedule; alternatively 400 mg/m² loading then 250 mg/m² weekly) · IV day 1 of each 14-d cycle · IV ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-2L-FOLFIRI-BEV
- Regimen
- FOLFIRI + Bevacizumab (or ± cetuximab if RAS-WT left-sided)
- Drugs + NSZU
- Irinotecan (DRUG-IRINOTECAN) 180 mg/m² · IV day 1 of each 14-day cycle · IV ✓ NSZU covered
- Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 · IV ✓ NSZU covered
- 5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus + 2400 mg/m² CIV over 46h · Day 1 bolus, day 1-2 CIV · IV ✓ NSZU covered
- Bevacizumab (DRUG-BEVACIZUMAB) 5 mg/kg (FOLFIRI-bev variant) · IV day 1 of each 14-day cycle · IV ✓ NSZU covered
- Supportive care
- SUP-GCSF-NEUTROPENIA
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-3L-TAS102-BEV
- Regimen
- Trifluridine-Tipiracil + Bevacizumab (SUNLIGHT) — 3L+ mCRC
- 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
- Bevacizumab (DRUG-BEVACIZUMAB) 5 mg/kg · IV days 1, 15 of each 28-day cycle · IV ✓ NSZU covered
- Supportive care
- SUP-GCSF-NEUTROPENIA
- Reason
- Current-line alternative presented for HCP consideration
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 4 → branch IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB
- RF-CRC-HER2-AMP-ACTIONABLE ★ winner: HER2 amplification in metastatic colorectal cancer — IHC 3+ OR (IHC 2+ AND ISH amplified, HER2/CEP17 ≥2.0). Present in ~3% of mCRC, enriched in left-sided RAS-WT tumors. Treatment-defining for RAS-WT subset: tucatinib + trastuzumab (MOUNTAINEER ORR 38%, mPFS 8.2 mo, mOS 24.1 mo; FDA Jan 2023) as 2L+/3L+ standard; T-DXd (DESTINY-CRC01) as alternative for IHC 3+ heavily pretreated. Excludes RAS-mutant (MOUNTAINEER eligibility) and MSI-H (pembrolizumab supersedes). Distinct from BIO-HER2-SOLID composite IHC marker: this red-flag is the actionability gate that fires for the CRC HER2-amp + RAS-WT subset specifically.
SRC-NCCN-COLON-2025SRC-ESMO-COLON-2024SRC-MOUNTAINEER-STRICKLER-2022
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-BRAF-V600E | BRAF V600E mutation testing | Critical | histology | CSD Lab ✓ (code TBC) | aggressive |
| 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-DMMR-IHC | MMR proteins IHC (MLH1 / MSH2 / MSH6 / PMS2) | Critical | histology | CSD Lab ✓ (code TBC) | aggressive |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-MSI-PCR-OR-NGS | MSI status by PCR or NGS | Critical | histology | CSD Lab: M065
CSD Lab ✓ (code TBC) | aggressive |
| TEST-RAS-EXTENDED | RAS extended panel (KRAS exons 2-4 + NRAS exons 2-4) | Critical | histology | CSD Lab: M065 | all tracks |
| TEST-CEA | CEA | Standard | lab | — | 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 |
| TEST-NGS-COMPREHENSIVE | Comprehensive NGS tumor panel (DNA + RNA, ≥300 genes) | Desired | histology | CSD Lab: M065 | aggressive |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- BRAF V600E mutation in mCRC: ~8-10% prevalence, poor prognosis (median OS halved vs BRAF-WT on standard chemo). Cetuximab/panitumumab ineffective. Encorafenib + cetuximab (BEACON CRC) is preferred 2L+; some 1L data favor FOLFOXIRI + bev intensification in MSS BRAF-mutant.
~30% of BRAF-mutant CRC are MSI-H — RF-CRC-MSI-H-ACTIONABILITY takes precedence (immunotherapy-track outranks chemo-intensification). In MSS BRAF-V600E mutants (the harder subgroup), TRIBE-2 / FOLFOXIRI+bev has ORR 56% but inferior to…
RF-CRC-BRAF-V600E-POOR-PROGNOSISSRC-NCCN-COLON-2025SRC-ESMO-COLON-2024 - Surgical emergency in CRC: complete bowel obstruction (closed-loop or large-bowel obstruction with competent ileocecal valve), perforation with peritonitis, or massive lower-GI bleed requiring transfusion. Mandates urgent surgery / interventional decompression BEFORE any systemic therapy decision; staging and biomarker work-up are deferred until patient is stabilized.
~10-30% of CRC presents with obstruction; ~3-8% with perforation. Self-expandable metal stent (SEMS) is bridge-to-surgery option for left-sided malignant obstruction in elective surgical candidates; emergency surgery for right-sided /…
RF-CRC-EMERGENCY-OBSTRUCTION-PERFORATIONSRC-NCCN-COLON-2025SRC-ESMO-COLON-2024 - Frailty/age profile precluding doublet-intensive or triplet chemo: ECOG ≥3, OR (age ≥80 + Charlson ≥3), OR composite (age ≥75 + albumin <3.0 + ≥2 comorbidities). Triggers de-escalation toward 5-FU/LV mono, capecitabine mono, or best supportive care.
IDEA pooled analysis: 3 mo CAPOX adjuvant non-inferior to 6 mo for low-risk (T1-3 N1) stage III — explicitly designed for elderly / fragile. FOCUS-2 trial: capecitabine ± oxaliplatin in elderly mCRC showed acceptable efficacy with reduced…
RF-CRC-FRAILTY-AGESRC-NCCN-COLON-2025SRC-ESMO-COLON-2024 - HER2 amplification in metastatic colorectal cancer — IHC 3+ OR (IHC 2+ AND ISH amplified, HER2/CEP17 ≥2.0). Present in ~3% of mCRC, enriched in left-sided RAS-WT tumors. Treatment-defining for RAS-WT subset: tucatinib + trastuzumab (MOUNTAINEER ORR 38%, mPFS 8.2 mo, mOS 24.1 mo; FDA Jan 2023) as 2L+/3L+ standard; T-DXd (DESTINY-CRC01) as alternative for IHC 3+ heavily pretreated. Excludes RAS-mutant (MOUNTAINEER eligibility) and MSI-H (pembrolizumab supersedes). Distinct from BIO-HER2-SOLID composite IHC marker: this red-flag is the actionability gate that fires for the CRC HER2-amp + RAS-WT subset specifically.
Hierarchy in 2L mCRC: MSI-H (KEYNOTE-164) > BRAF V600E (BEACON) > KRAS G12C (CodeBreaK 300) > HER2-amp + RAS-WT (MOUNTAINEER / DESTINY-CRC01) > EGFRi rechallenge > FOLFIRI + bev. Captured in ALGO-CRC-METASTATIC-2L decision tree. UA access…
RF-CRC-HER2-AMP-ACTIONABLESRC-NCCN-COLON-2025SRC-ESMO-COLON-2024SRC-MOUNTAINEER-STRICKLER-2022 - MSI-high / dMMR mCRC — treatment-defining biomarker. KEYNOTE-177 established pembrolizumab 1L over FOLFOX+bev (PFS 16.5 vs 8.2 mo). This RF intensifies toward the immunotherapy track and overrides the default RAS/BRAF-driven chemo algorithm.
MSI-H/dMMR ~5% of metastatic CRC, ~15% of stage II-III. Adjuvant setting — ICI not yet standard outside trials (NICHE/NICHE-2 promising for neoadjuvant ICI in non-metastatic dMMR colon — emerging paradigm). Lynch-syndrome-driven dMMR…
RF-CRC-MSI-H-ACTIONABILITYSRC-NCCN-COLON-2025SRC-ESMO-COLON-2024 - Metastatic colorectal cancer with RAS wild-type status: KRAS exon 2 (codons 12, 13), exon 3 (codons 59, 61), exon 4 (codons 117, 146) AND NRAS exon 2/3/4 ALL wild-type by NGS or extended-RAS PCR. Defines the ~50% of mCRC eligible for anti-EGFR monoclonal antibody therapy (cetuximab, panitumumab) when combined with chemotherapy backbone. Left-sided RAS-WT mCRC particularly benefits from 1L anti-EGFR + FOLFOX/ FOLFIRI (CALGB/SWOG-80405, FIRE-3, PRIME, CRYSTAL — survival benefit driven by left-sided primaries; right-sided RAS-WT does NOT benefit and routes to bevacizumab + chemo).
Sidedness modifier: left-sided primary (splenic flexure to rectum) + RAS-WT — anti-EGFR + chemo strongly preferred (mOS ~38 mo with cetux+ FOLFOX vs ~33 mo with bev+FOLFOX, FIRE-3 left-sided). Right-sided primary (cecum to transverse) +…
RF-CRC-RAS-WTSRC-NCCN-COLON-2025SRC-ESMO-COLON-2024
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
Aggressive plan (IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB)
- Do NOT prescribe in RAS-mutant patients — MOUNTAINEER excluded RAS-mut; benefit substantially reduced.
- Do NOT initiate without baseline LVEF — trastuzumab cardiotoxicity surveillance protocol mandatory (q3 mo).
- Do NOT ignore early diarrhea management — tucatinib loperamide protocol; reduce dose if Grade ≥3.
- Do NOT combine with strong CYP3A4 inducers — tucatinib levels reduced significantly.
- Do NOT continue with LVEF drop ≥10% absolute OR LVEF <50% — hold trastuzumab; cardiology consult.
- Do NOT confirm the plan without funding pathway — tucatinib not registered in UA.
Aggressive plan (IND-CRC-METASTATIC-2L-MSI-H-PEMBRO)
- Do NOT prescribe without verified MSI-H/dMMR status — false-positive MSI may cause hyperprogression.
- Do NOT continue pembrolizumab through Grade 3+ irAE without specialist consultation + steroid taper.
- Do NOT combine with chronic high-dose corticosteroids — pharmacodynamic blunting of ICI.
- Do NOT prescribe in active autoimmune disease without rheumatology / endocrinology MDT.
- Do NOT discontinue therapy at tumor pseudoprogression (early flare-up imaging) without biopsy / iRECIST evaluation.
- Do NOT confirm the plan without funding pathway — pembrolizumab not NSZU-reimbursed for CRC.
Aggressive plan (IND-CRC-METASTATIC-2L-BRAF-BEACON)
- Do NOT use anti-EGFR (cetuximab/panitumumab) MONOTHERAPY in BRAF V600E — minimal benefit (BEACON control arm performance)
- Do NOT skip skin dermatology surveillance (BRAFi class effect — new SCC + melanoma risk)
- Do NOT continue through QTcF >500 ms without dose hold + ECG
Aggressive plan (IND-CRC-METASTATIC-2L-KRAS-G12C-SOTORASIB-CETUXIMAB)
- Do NOT prescribe without verified KRAS G12C status — other KRAS variants (G12D, G12V, G13D) do not respond.
- Do NOT use sotorasib in combination with PPI — significantly reduces absorption (acid-dependent dissolution).
- Do NOT initiate without baseline LFTs — sotorasib hepatotoxicity ~25% transaminase elevation.
- Do NOT combine with strong CYP3A4 inducers — sotorasib levels reduced.
- Do NOT ignore acneiform rash management — cetuximab requires tetracycline + topical clindamycin protocol.
- Do NOT continue sotorasib with Grade 3+ hepatic AE — hold + reduce dose or discontinue.
- Do NOT confirm the plan without funding pathway — sotorasib not registered in UA; cetuximab not reimbursed for RAS-mut.
Aggressive plan (IND-CRC-METASTATIC-2L-HER2-AMP-T-DXD)
- Do NOT prescribe in baseline ILD/pneumonitis OR prior amiodarone-induced lung disease — high re-activation risk.
- Do NOT ignore new respiratory symptoms (cough, dyspnea) — STOP T-DXd, urgent CT, low-threshold steroids.
- Do NOT prescribe in RAS-mutant patients — DESTINY-CRC01 excluded RAS-mut.
- Do NOT initiate without baseline LVEF — trastuzumab moiety cardiotoxicity surveillance.
- Do NOT combine with other DNA topo-I inhibitors (irinotecan, topotecan) — overlapping toxicity.
- Do NOT continue with Grade 2+ pneumonitis — permanently discontinue T-DXd.
- Do NOT confirm the plan without funding pathway — T-DXd not NSZU-reimbursed for CRC.
Aggressive plan (IND-CRC-METASTATIC-2L-EGFRI-RECHALLENGE)
- Do NOT prescribe rechallenge without prior anti-EGFR response (PR+ OR SD ≥6 mo) — inadequate selection.
- Do NOT use rechallenge immediately after prior anti-EGFR (without intervening line) — clonal selection has not yet decayed.
- Do NOT ignore RAS-WT confirmation — baseline RAS-mut patients should not receive rechallenge.
- Do NOT initiate in known BRAF V600E — preferred encorafenib + cetuximab (BEACON).
- Do NOT ignore acneiform rash management — tetracycline + topical clindamycin protocol.
- Do NOT confirm rechallenge without funding pathway — cetuximab not NSZU-reimbursed for non-1L.
Standard plan (IND-CRC-METASTATIC-2L-FOLFIRI-BEV)
- Do NOT use anti-EGFR in RAS-mutant patients — minimal benefit + potential harmful effect.
- Do NOT initiate within 28 days of major surgery — bevacizumab perforation/dehiscence risk.
- Do NOT continue bevacizumab in uncontrolled HTN >160/100 — cerebrovascular risk.
- Do NOT ignore UGT1A1 testing if available — *28/*28 risk of severe neutropenia + diarrhea.
- Do NOT skip the loperamide protocol for irinotecan-induced delayed diarrhea — fatal dehydration possible.
- Do NOT use in high-risk varices / active hemoptysis (bevacizumab).
- Do NOT confirm anti-EGFR without funding — cetuximab / panitumumab not reimbursed for 2L.
Standard plan (IND-CRC-METASTATIC-3L-TAS102-BEV)
- Do NOT prescribe with ANC <1500 or platelets <75K at cycle start — myelosuppression likely Grade 3+.
- Do NOT escalate dose without count recovery cycle-to-cycle — neutropenia is dose-limiting.
- Do NOT initiate bevacizumab within 28 days of major surgery.
- Do NOT continue bevacizumab in uncontrolled HTN.
- Do NOT use in active hemoptysis / GI bleeding.
- Do NOT prescribe with ECOG 3-4 — toxicity profile exceeds frail patient tolerance.
- Do NOT confirm the plan without funding pathway for TAS-102.
- Do NOT forget to reduce dose when CrCl 30-59 (20 mg/m² BID).
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · Tucatinib + Trastuzumab (MOUNTAINEER, HER2+ RAS-WT mCRC)
21-day cycles × Until progression / unacceptable toxicity
Aggressive plan
Induction · Pembrolizumab monotherapy (MSI-H mCRC 1L)
21-day cycles × Until progression / unacceptable toxicity / max 35 cycles per KEYNOTE-177
Aggressive plan
Induction · Encorafenib + Cetuximab (BEACON CRC)
28-day cycles × Until progression / unacceptable toxicity
Aggressive plan
Induction · Sotorasib + Cetuximab (CodeBreaK 300, KRAS G12C+ mCRC)
14-day cycles × Until progression / unacceptable toxicity
Aggressive plan
Induction · Trastuzumab-deruxtecan monotherapy (DESTINY-CRC01, HER2+ mCRC)
21-day cycles × Until progression / unacceptable toxicity / ILD
Aggressive plan
Induction · FOLFOX + Cetuximab
14-day cycles × Until progression / unacceptable toxicity
Standard plan
Induction · FOLFIRI + Bevacizumab (or ± cetuximab if RAS-WT left-sided)
14-day cycles × Until progression / unacceptable toxicity (mCRC 2L+)
Standard plan
Induction · Trifluridine-Tipiracil + Bevacizumab (SUNLIGHT) — 3L+ mCRC
28-day cycles × Until progression / unacceptable toxicity
MDT brief
Discussion questions (5, 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-BRAF-V600E
What is the status of BRAF V600E mutation (BIO-BRAF-V600E)? It is required by track(s): IND-CRC-METASTATIC-2L-BRAF-BEACON. Expected value: positive.
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.
→ molecular_geneticist
OQ-BIOMARKER-KRAS-G12C
What is the status of KRAS G12C mutation (BIO-KRAS-G12C)? It is required by track(s): IND-CRC-METASTATIC-2L-KRAS-G12C-SOTORASIB-CETUXIMAB. Expected value: G12C-positive (covalent inhibitor target).
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.
→ molecular_geneticist
OQ-BIOMARKER-MSI-STATUS
What is the status of Microsatellite instability status (BIO-MSI-STATUS)? It is required by track(s): IND-CRC-METASTATIC-2L-MSI-H-PEMBRO. Expected value: MSI-H or dMMR (treatment-defining; supersedes other 2L choices).
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.
→ molecular_geneticist
OQ-BIOMARKER-RAS-MUTATION
What is the status of RAS mutation status (KRAS / NRAS exons 2-4) (BIO-RAS-MUTATION)? It is required by track(s): IND-CRC-METASTATIC-2L-EGFRI-RECHALLENGE. Expected value: RAS wild-type at baseline AND (preferably) RAS-WT confirmed on ctDNA at rechallenge timepoint (CHRONOS biomarker selection).
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.
→ molecular_geneticist
MDT talk tree (7 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | molecular_geneticist | Biomarker status | What is the status of BRAF V600E mutation (BIO-BRAF-V600E)? It is required by track(s): IND-CRC-METASTATIC-2L-BRAF-BEACON. Expected value: positive. |
| 3 | molecular_geneticist | Biomarker status | What is the status of KRAS G12C mutation (BIO-KRAS-G12C)? It is required by track(s): IND-CRC-METASTATIC-2L-KRAS-G12C-SOTORASIB-CETUXIMAB. Expected value: G12C-positive (covalent inhibitor target). |
| 4 | molecular_geneticist | Biomarker status | What is the status of Microsatellite instability status (BIO-MSI-STATUS)? It is required by track(s): IND-CRC-METASTATIC-2L-MSI-H-PEMBRO. Expected value: MSI-H or dMMR (treatment-defining; supersedes other 2L choices). |
| 5 | molecular_geneticist | Biomarker status | What is the status of RAS mutation status (KRAS / NRAS exons 2-4) (BIO-RAS-MUTATION)? It is required by track(s): IND-CRC-METASTATIC-2L-EGFRI-RECHALLENGE. Expected value: RAS wild-type at baseline AND (preferably) RAS-WT confirmed on ctDNA at rechallenge timepoint (CHRONOS biomarker selection). |
| 6 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| 7 | social_worker_case_manager | Specialist review | Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed. |
Skills (recommended) — for consideration (3)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Owns: OQ-BIOMARKER-BRAF-V600E, OQ-BIOMARKER-KRAS-G12C, OQ-BIOMARKER-MSI-STATUS, OQ-BIOMARKER-RAS-MUTATION
- 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: 1/5 known (20%), 4 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-BLM-CONFIRMED-CARRIER, RF-CASCADE-FAP-FDR-POSITIVE, RF-CASCADE-LYNCH-FDR-POSITIVE, RF-CHEK2-CONFIRMED-CARRIER, RF-CHEK2-FAMILY-HISTORY-SUSPICION, RF-CHRONIC-IBD-CROHNS-SPECIFIC-PREVENTION, RF-CHRONIC-SEVERE-OBESITY-BMI40-PREVENTION, RF-CHRONIC-T2DM-CANCER-RISK-PREVENTION, RF-CMMRD-CONFIRMED-CARRIER, RF-COWDEN-CONFIRMED-CARRIER, RF-COWDEN-FAMILY-HISTORY-SUSPICION, RF-CRC-BRAF-V600E-POOR-PROGNOSIS, RF-CRC-EMERGENCY-OBSTRUCTION-PERFORATION, RF-CRC-FRAILTY-AGE, RF-CRC-HER2-AMP-ACTIONABLE, RF-CRC-INFECTION-SCREENING, RF-CRC-MSI-H-ACTIONABILITY, RF-CRC-OLIGOMET-LIVER-DEFINITION, RF-CRC-RAS-MUTANT, RF-CRC-RAS-WT, RF-CRC-TRANSFORMATION-PROGRESSION, RF-CRONKHITE-CANADA-CONFIRMED, RF-FAP-CONFIRMED-CARRIER, RF-FAP-FAMILY-HISTORY-SUSPICION, RF-IBD-CRC-PREVENTION, RF-JPS-CONFIRMED-CARRIER, RF-LIFESTYLE-ALCOHOL-CANCER-PREVENTION, RF-LIFESTYLE-HIGH-RED-MEAT-CRC-PREVENTION, RF-LIFESTYLE-LOW-CALCIUM-VIT-D-CRC-PREVENTION, RF-LIFESTYLE-LOW-FIBER-CRC-PREVENTION, RF-LIFESTYLE-LOW-MEDITERRANEAN-DIET-PREVENTION, RF-LIFESTYLE-OBESITY-CANCER-PREVENTION, RF-LIFESTYLE-PROCESSED-MEAT-PREVENTION, RF-LIFESTYLE-RED-MEAT-HIGH-INTAKE-PREVENTION, RF-LIFESTYLE-SEDENTARY-PREVENTION, RF-LIFESTYLE-SUGARY-BEVERAGES-PREVENTION, RF-LYNCH-CONFIRMED-CARRIER, RF-LYNCH-FAMILY-HISTORY-SUSPICION, RF-OCC-FIREFIGHTER-PREVENTION, RF-PEUTZ-JEGHERS-CONFIRMED-CARRIER, RF-PEUTZ-JEGHERS-FAMILY-HISTORY-SUSPICION, RF-PSC-CHOLANGIOCARCINOMA-PREVENTION
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|
BIO-BRAF-V600E | BRAF V600E mutation | molecular_geneticist | no | IND-CRC-METASTATIC-2L-BRAF-BEACON | Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive |
BIO-KRAS-G12C | KRAS G12C mutation | molecular_geneticist | no | IND-CRC-METASTATIC-2L-KRAS-G12C-SOTORASIB-CETUXIMAB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: G12C-positive (covalent inhibitor target) |
BIO-MSI-STATUS | Microsatellite instability status | molecular_geneticist | no | IND-CRC-METASTATIC-2L-MSI-H-PEMBRO | Verify result, method, specimen, and report date before sign-off. Expected/constraint: MSI-H or dMMR (treatment-defining; supersedes other 2L choices) |
BIO-RAS-MUTATION | RAS mutation status (KRAS / NRAS exons 2-4) | molecular_geneticist | no | IND-CRC-METASTATIC-2L-EGFRI-RECHALLENGE | Verify result, method, specimen, and report date before sign-off. Expected/constraint: RAS wild-type at baseline AND (preferably) RAS-WT confirmed on ctDNA at rechallenge timepoint (CHRONOS biomarker selection) |
Technical MDT skill metadata (3/16 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-CRC01-SIENA-2021: Trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial (2021)
- SRC-ESMO-COLON-2024: ESMO CRC Clinical Practice Guideline (2024)
- SRC-KEYNOTE-164-LE-2020: Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer (KEYNOTE-164) (2020)
- SRC-KEYNOTE-177-ANDRE-2020: Pembrolizumab versus Chemotherapy for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer (2020)
- SRC-NCCN-COLON-2025: NCCN Colon / Rectal Cancer (v.4.2025)
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 | |
| NCT07540572 | A Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of IDE574 Therapy in Adult Participants With Advanced Solid Tumors | PHASE1 | RECRUITING | — | Biomarker: unclear Phase 1 only Surrogate endpoint only Single country | |
| NCT07192068 | Clinical Trial Evaluating the Activity of Zanidatamab for the Treatment of Patients With Solid Tumors With an Alteration of the HER2 Gene. | PHASE2 | RECRUITING | — | Biomarker: unclear Surrogate endpoint only Single country | |
| NCT05059444 | ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation | N/A | RECRUITING | — | — | |
| NCT07589517 | Dual-Targeting CAR-NK Cells in Biomarker-Selected Advanced Colorectal Cancer | PHASE1 / PHASE2 | RECRUITING | — | Biomarker: unclear Small N (<50) Surrogate endpoint only Single country | |
| NCT07318805 | A Study to Learn About the Study Medicine Called PF-08032562 in People With Advanced or Metastatic Solid Tumors | PHASE1 | RECRUITING | — | Phase 1 only Surrogate endpoint only Single country | |
| NCT06500052 | A Study of BL-M17D1 in Patients With Locally Advanced or Metastatic HER2 Positive/Lower Expression Gastrointestinal Cancer and Other Solid Tumors | PHASE1 | RECRUITING | — | Biomarker: enriched Phase 1 only Small N (<50) Single country | |
| NCT07630961 | Phase I Study of JFI447 [68Ga]Ga-DFC413 and Comparison to FFG233 [68Ga]Ga-NNS309 in Patients With Solid Tumors | PHASE1 | RECRUITING | — | Biomarker: unclear Phase 1 only Single country | |
| NCT07462650 | Dual-Target CAR-NK Cells for Biomarker-Selected Advanced Colorectal Cancer | PHASE1 / PHASE2 | RECRUITING | — | Biomarker: unclear Small N (<50) Surrogate endpoint only Single country | |
| NCT03740256 | Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR VST, Advanced HER2 Positive Solid Tumors | PHASE1 | RECRUITING | — | Biomarker: enriched Phase 1 only Small N (<50) Single country | |
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 Tucatinib + Trastuzumab (MOUNTAINEER, HER2+ RAS-WT mCRC) (REG-TUCATINIB-TRASTUZUMAB-CRC) 1/2 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Pembrolizumab monotherapy (MSI-H mCRC 1L) (REG-PEMBROLIZUMAB-MSI-MONO) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Encorafenib + Cetuximab (BEACON CRC) (REG-ENCORAFENIB-CETUXIMAB) 1/2 component drug(s) not on NSZU formulary | ✓ registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Sotorasib + Cetuximab (CodeBreaK 300, KRAS G12C+ mCRC) (REG-SOTORASIB-CETUXIMAB-CRC) 1/2 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Trastuzumab-deruxtecan monotherapy (DESTINY-CRC01, HER2+ mCRC) (REG-TRASTUZUMAB-DERUXTECAN-CRC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan FOLFOX + Cetuximab (REG-FOLFOX-CETUX) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan FOLFIRI + Bevacizumab (or ± cetuximab if RAS-WT left-sided) (REG-FOLFIRI-BEV) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Trifluridine-Tipiracil + Bevacizumab (SUNLIGHT) — 3L+ mCRC (REG-TRIFLURIDINE-TIPIRACIL-BEV) 1/2 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 · NCT07540572 A Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of IDE574 Therapy in Adult Participants With Advanced Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07192068 Clinical Trial Evaluating the Activity of Zanidatamab for the Treatment of Patients With Solid Tumors With an Alteration of the HER2 Gene. 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 · NCT07589517 Dual-Targeting CAR-NK Cells in Biomarker-Selected Advanced Colorectal Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07318805 A Study to Learn About the Study Medicine Called PF-08032562 in People With Advanced or Metastatic Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06500052 A Study of BL-M17D1 in Patients With Locally Advanced or Metastatic HER2 Positive/Lower Expression Gastrointestinal Cancer and Other Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07630961 Phase I Study of JFI447 [68Ga]Ga-DFC413 and Comparison to FFG233 [68Ga]Ga-NNS309 in Patients With Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07462650 Dual-Target CAR-NK Cells for Biomarker-Selected Advanced Colorectal Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT03740256 Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR VST, Advanced HER2 Positive 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.