OpenOnco · Treatment Plan

Treatment plan — Colorectal carcinoma

PLAN-CRC-MET-2L-FOLFIRI-BEV-001-V1 · v1 · 2026-05-13

Patient

CRC-MET-2L-FOLFIRI-BEV-001 · Algorithm: ALGO-CRC-METASTATIC-2L

DiagnosisColorectal carcinoma

MOH / ICD-10C18-C20

ICD-O-38140/3; C18, C19, C20

StageIV

Histologyadenocarcinoma

Clinical significance of mutations (ESCAT)

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

✅ Covered biomarkers (matched in KB)

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
BIO-RAS-MUTATION	KRAS A146T	IV	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS A146T — rare, anti-EGFR contraindication marker. No targeted therapy.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	KRAS exon 3 codon 59/61	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS exon 3 codon 59/61 in mCRC — extended-RAS WT criterion fails; anti-EGFR (cetuximab/panitumumab) contraindicated. Standard chemo ± bevacizumab.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024
BIO-RAS-MUTATION	KRAS exon 4 codon 117/146	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS exon 4 codon 117/146 in mCRC — extended-RAS WT criterion fails; anti-EGFR (cetuximab/panitumumab) contraindicated. Standard chemo ± bevacizumab.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024
BIO-RAS-MUTATION	KRAS G12D	IV	Molecular evidence option SRC-CIVIC: Level B (Supports, Better Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G12D in mCRC predicts anti-EGFR resistance. No approved targeted therapy 2026; trial-only (MRTX1133, RMC-9805 + cetuximab combos).	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	KRAS G12V	IV	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G12V in mCRC — anti-EGFR contraindication marker, no targeted therapy. Standard chemo ± anti-VEGF.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	KRAS G12 (any)	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G12 (any) in mCRC — extended-RAS WT criterion fails; anti-EGFR (cetuximab/panitumumab) contraindicated. Standard chemo ± bevacizumab.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024
BIO-RAS-MUTATION	KRAS G13D	IV	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G13D in mCRC — historical signal of partial cetuximab response (De Roock 2010) was not confirmed prospectively. Treat as RAS-mut, anti-EGFR contraindicated.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	KRAS G13 (any non-G13C)	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G13 (any non-G13C) in mCRC — extended-RAS WT criterion fails; anti-EGFR (cetuximab/panitumumab) contraindicated. Standard chemo ± bevacizumab.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024
BIO-RAS-MUTATION	KRAS Q61 (any)	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS Q61 (any) in mCRC — extended-RAS WT criterion fails; anti-EGFR (cetuximab/panitumumab) contraindicated. Standard chemo ± bevacizumab.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024
BIO-RAS-MUTATION	NRAS G12	IB	Molecular evidence option SRC-CIVIC: Level B (Supports, N/A) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response)	NRAS codon 12 mutation in mCRC — extended RAS WT criterion fails; anti-EGFR contraindicated.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	NRAS G13	IB	Molecular evidence option SRC-CIVIC: Level B (Supports, N/A) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response)	NRAS codon 13 in mCRC — anti-EGFR contraindicated.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	NRAS Q61K	IB	Molecular evidence option SRC-CIVIC: Level B (Supports, N/A) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	NRAS Q61K in mCRC — anti-EGFR contraindication.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	NRAS Q61R	IB	Molecular evidence option SRC-CIVIC: Level B (Supports, N/A) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	NRAS Q61R in mCRC — anti-EGFR (cetuximab/panitumumab) contraindication. Standard chemo ± bev; no NRAS-selective drug.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024

⚠️ Not included in plan

Biomarker	Status
BIO-MSI-STATUS	BIO definition in KB; no ESCAT BMA entry — verify with clinician
BIO-BRAF-V600E	Excluded (negative)
KRAS	Not in KB — ask clinician to verify

Primary current-line option

Standard plan

★ DEFAULT

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

Primary current-line option selected by ALGO-CRC-METASTATIC-2L at step 6; branch-driving red flag: RF-CRC-TRANSFORMATION-PROGRESSION.

Other current-line alternatives (6 tracks)

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

Aggressive plan

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

Aggressive plan

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

Aggressive plan

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

Aggressive plan

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

Current-line alternative presented for HCP consideration

Aggressive plan

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

Aggressive plan

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

Why this branch was chosen

Triggers from the patient profile that fired and drove the chosen branch.

Step 6 → branch IND-CRC-METASTATIC-2L-FOLFIRI-BEV

RF-CRC-TRANSFORMATION-PROGRESSION ★ winner: Rapid progression in CRC: relapse within ≤6 months of completing adjuvant chemo (oxaliplatin-resistant phenotype), new peritoneal carcinomatosis with ascites + obstruction, OR rapid LDH/CEA doubling (>50% rise over 4-8 weeks). Alters 2L+ regimen choice + may contraindicate oxaliplatin re-introduction. SRC-NCCN-COLON-2025SRC-ESMO-COLON-2024

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. RF-CRC-BRAF-V600E-POOR-PROGNOSIS
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. RF-CRC-EMERGENCY-OBSTRUCTION-PERFORATION
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. RF-CRC-FRAILTY-AGE
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. RF-CRC-HER2-AMP-ACTIONABLE
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. RF-CRC-MSI-H-ACTIONABILITY
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). RF-CRC-RAS-WT

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-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.

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-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-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.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · FOLFIRI + Bevacizumab (or ± cetuximab if RAS-WT left-sided)

14-day cycles × Until progression / unacceptable toxicity (mCRC 2L+)

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 · Tucatinib + Trastuzumab (MOUNTAINEER, HER2+ RAS-WT mCRC)

21-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

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-HER2-SOLID
What is the status of HER2 status (solid tumors — gastric/GEJ/CRC scoring) (BIO-HER2-SOLID)? It is required by track(s): IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB, IND-CRC-METASTATIC-2L-HER2-AMP-T-DXD. Expected value: amplified — IHC 3+ OR (IHC 2+ AND ISH+).
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 (5 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 HER2 status (solid tumors — gastric/GEJ/CRC scoring) (BIO-HER2-SOLID)? It is required by track(s): IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB, IND-CRC-METASTATIC-2L-HER2-AMP-T-DXD. Expected value: amplified — IHC 3+ OR (IHC 2+ AND ISH+).
3	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
4	molecular_geneticist	Specialist review	Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
5	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.
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: 4/5 known (80%), 1 missing, 0 default-track gaps
Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-CRC-EMERGENCY-OBSTRUCTION-PERFORATION, RF-CRC-FRAILTY-AGE, RF-CRC-HER2-AMP-ACTIONABLE, RF-CRC-INFECTION-SCREENING, RF-CRC-OLIGOMET-LIVER-DEFINITION, RF-CRC-RAS-WT, RF-CRC-TRANSFORMATION-PROGRESSION

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-HER2-SOLID`	HER2 status (solid tumors — gastric/GEJ/CRC scoring)	pathologist	no	IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB, IND-CRC-METASTATIC-2L-HER2-AMP-T-DXD	Verify result, method, specimen, and report date before sign-off. Expected/constraint: amplified — IHC 3+ OR (IHC 2+ AND ISH+)

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	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-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: 2026-05-13.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT05727163	FOLFOX Via HAI Plus Intravenous Irinotecan With or Without Bevacizumab Versus Systemic FOLFOXIRI With or Without Bevacizumab in Initially Unresectable RAS-mutated CRLM Patients	PHASE2	RECRUITING	Sun Yat-sen University	—	Surrogate endpoint only Single country
NCT02885753	Systemic Oxaliplatin or Intra-arterial Chemotherapy Combined With LV5FU2 +/- Irinotecan and an Target Therapy in First Line Treatment of Metastatic Colorectal Cancer Restricted to the Liver	PHASE3	RECRUITING	Federation Francophone de Cancerologie Digestive	—	Biomarker: enriched Surrogate endpoint only
NCT06226857	Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer	PHASE3	RECRUITING	City Clinical Oncology Hospital No 1	—	Surrogate endpoint only Single country
NCT06445062	Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors	PHASE1 / PHASE2	RECRUITING	Revolution Medicines, Inc.	—	Biomarker: enriched Single country
NCT06895031	Study of JYP0015 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS	PHASE2	RECRUITING	Guangzhou JOYO Pharma Co., Ltd	—	Biomarker: enriched Surrogate endpoint only Single country
NCT06440902	Exploration of Therapeutic Strategies for NeoRAS Wild-type Metastatic Colorectal Cancer Based on Circulating Tumor DNA	PHASE2	RECRUITING	Fudan University	—	Biomarker: enriched Single country
NCT06218810	Cadonilimab in Combination With Bevacizumab and FOLFOX Regimen for the First-Line Treatment of Advanced Unresectable MSS-Type, RAS-Mutated Metastatic Colorectal Cancer	PHASE2	RECRUITING	Fudan University	—	Surrogate endpoint only Single country
NCT06229340	Leflunomide or Combination of MEK Inhibitor and Hydroxychloroquine for Refractory Patients With RAS Mutations	PHASE2	RECRUITING	N.N. Petrov National Medical Research Center of Oncology	—	Biomarker: enriched Small N (<50) Surrogate endpoint only Single country
NCT05861505	COLLISION RELAPSE Trial	PHASE3	RECRUITING	Amsterdam UMC, location VUmc	—	Single country
NCT07349537	Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors	PHASE1	RECRUITING	Revolution Medicines, Inc.	—	Biomarker: enriched Phase 1 only 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
Standard plan FOLFIRI + Bevacizumab (or ± cetuximab if RAS-WT left-sided) (REG-FOLFIRI-BEV)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
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 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 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
Trial · NCT05727163 FOLFOX Via HAI Plus Intravenous Irinotecan With or Without Bevacizumab Versus Systemic FOLFOXIRI With or Without Bevacizumab in Initially Unresectable RAS-mutated CRLM Patients No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT02885753 Systemic Oxaliplatin or Intra-arterial Chemotherapy Combined With LV5FU2 +/- Irinotecan and an Target Therapy in First Line Treatment of Metastatic Colorectal Cancer Restricted to the Liver No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06226857 Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06445062 Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06895031 Study of JYP0015 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06440902 Exploration of Therapeutic Strategies for NeoRAS Wild-type Metastatic Colorectal Cancer Based on Circulating Tumor DNA No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06218810 Cadonilimab in Combination With Bevacizumab and FOLFOX Regimen for the First-Line Treatment of Advanced Unresectable MSS-Type, RAS-Mutated Metastatic Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06229340 Leflunomide or Combination of MEK Inhibitor and Hydroxychloroquine for Refractory Patients With RAS Mutations No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05861505 COLLISION RELAPSE Trial No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07349537 Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant 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: 2026-05-13.

plan_id: PLAN-CRC-MET-2L-FOLFIRI-BEV-001-V1 | version: 1 | generated: 2026-05-13T10:01:52.954316+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.