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Living with cancer·Standard of care

HER2-amplified colorectal cancer: the decisions you may face

Cancer page →Second-opinion finder →

3 treatment settings, 3 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.

Advanced, first line

Metastatic, RAS wild-type, previously treated

4 optionsCompare side by side →

Tucatinib plus trastuzumab (MOUNTAINEER); trastuzumab plus pertuzumab or lapatinib where tucatinib is unavailable.

Guideline
NCCN Guidelines: Colon Cancer
The options, in plain words
TucatinibApprovedSmall-molecule kinase inhibitor (HER2)

A HER2-selective pill that works in the brain, for HER2-positive breast cancer with brain metastases.

TrastuzumabApprovedMonoclonal antibody (anti-HER2)

The first targeted antibody for a solid tumour (1998), which turned HER2-positive breast cancer from the worst subtype into one of the most treatable.

PertuzumabApprovedMonoclonal antibody (anti-HER2, dimerisation domain)

A second HER2 antibody that binds a different spot from trastuzumab, blocking HER2 from pairing with HER3; together they extended survival by 16 months in CLEOPATRA.

HER2 tyrosine kinase inhibitorsApproved

Small pills that block HER2 from inside the cell, complementing antibody drugs; tucatinib is notable for working against brain metastases.

  • Oral
  • Activity against brain metastases
  • Combine with antibodies and chemotherapy
The evidence behind it
The main trade-offs on record
Tucatiniball recorded rates →
  • Reduce to 200 mg twice daily in severe impairment.
HER2 tyrosine kinase inhibitors
  • Diarrhoea, especially with neratinib and lapatinib
  • Resistance through HER2 mutations and pathway bypass
Questions to ask about this decision
  1. Between Tucatinib, Trastuzumab, Pertuzumab and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in MOUNTAINEER & MOUNTAINEER-03, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCCN Guidelines: Colon Cancer), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (metastatic, ras wild-type, previously treated), which of the standard options do you recommend and why?
    Why: Guideline options include: Tucatinib plus trastuzumab (MOUNTAINEER); trastuzumab plus pertuzumab or lapatinib where tucatinib is unavailable.
  7. Am I a candidate for Tucatinib, Trastuzumab, Pertuzumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  8. How do the results of MOUNTAINEER & MOUNTAINEER-03 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

After HER2 antibodies, or with RAS mutation

2 options

Trastuzumab deruxtecan (DESTINY-CRC02; tumour-agnostic approval for immunohistochemistry 3+), watching for pneumonitis.

Guideline
NCCN Guidelines: Colon Cancer
The options, in plain words
Trastuzumab deruxtecanApprovedADC

Trastuzumab deruxtecan (Enhertu) is the most successful ADC ever. It redefined HER2 by working in tumours with only tiny amounts of the protein, and in 2026 moved into early-stage breast cancer.

Antibody-drug conjugate (ADC)Approved3rd generation dominant; 4th emerging

An antibody-drug conjugate is an antibody that homes to a protein on the tumour cell, is swallowed, and releases a chemotherapy payload inside it. That widens chemotherapy's safe dose window about a hundredfold, which is why payloads too toxic to give alone can be used, though lung inflammation, neutropenia and eye toxicity from the payload still occur.

  • Widens the therapeutic index of chemotherapy 100-fold
  • Works in 'low' antigen expressers via bystander effect
  • Active after chemotherapy resistance
The evidence behind it
The main trade-offs on record
Trastuzumab deruxtecanall recorded rates →
Side effectAny gradeGrade 3+
Neutropenia · DESTINY-Breast03/04; all-grade rates ≥20% per label-18%
Nausea · DESTINY-Breast03/04; all-grade rates ≥20% per label-7%
Anaemia · DESTINY-Breast03/04; all-grade rates ≥20% per label-7%
Fatigue · DESTINY-Breast03/04; all-grade rates ≥20% per label-6%
  • Interstitial lung disease in 10-15%: hold for any respiratory symptom and image; permanently discontinue for grade 2 or above. Moderately emetogenic: three-drug prophylaxis.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Antibody-drug conjugate (ADC)
  • Payload-class toxicities are systemic (neutropenia, ILD, neuropathy, ocular)
  • Resistance via antigen loss, efflux, TOP1/SLFN11 changes
  • Manufacturing cost
Questions to ask about this decision
  1. Between Trastuzumab deruxtecan and Antibody-drug conjugate (ADC), which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in DESTINY-CRC02, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. Which side effects of Trastuzumab deruxtecan are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  5. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  6. Does your recommendation follow the current guideline (NCCN Guidelines: Colon Cancer), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  7. For my situation (after her2 antibodies, or with ras mutation), which of the standard options do you recommend and why?
    Why: Guideline options include: Trastuzumab deruxtecan (DESTINY-CRC02; tumour-agnostic approval for immunohistochemistry 3+), watching for pneumonitis.
  8. Am I a candidate for Trastuzumab deruxtecan, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  9. How do the results of DESTINY-CRC02 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Advanced, first line

Metastatic, first line

3 optionsCompare side by side →

Standard doublet chemotherapy with bevacizumab; anti-EGFR antibodies are less effective in HER2-amplified tumours; tucatinib-trastuzumab-FOLFOX is under test in MOUNTAINEER-03.

Guideline
NCCN Guidelines: Colon Cancer
The options, in plain words
FOLFOX (5-FU, leucovorin, oxaliplatin)Standard of careCytotoxic regimen

FOLFOX is the workhorse chemotherapy combination for bowel cancer, used after surgery to cure and in advanced disease as the backbone that targeted drugs are added to.

FOLFIRI (5-FU, leucovorin, irinotecan)Standard of careCytotoxic regimen

FOLFIRI is the other backbone bowel-cancer chemotherapy, swapping oxaliplatin for irinotecan. Used first or second line and, since 2026, with the BRAF combination.

BevacizumabApprovedMonoclonal antibody (anti-VEGF)

Bevacizumab is a humanised antibody that soaks up VEGF-A, the signal tumours use to grow new blood vessels. Approved in 2004, it partners chemotherapy in colorectal, ovarian, cervical, lung, kidney and liver cancer and glioblastoma, and adds to trifluridine/tipiracil in late-line bowel cancer; hypertension, protein in the urine and bleeding are its characteristic side effects.

The evidence behind it
The main trade-offs on record

No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.

Questions to ask about this decision
  1. Between FOLFOX (5-FU, leucovorin, oxaliplatin), FOLFIRI (5-FU, leucovorin, irinotecan) and Bevacizumab, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCCN Guidelines: Colon Cancer), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (metastatic, first line), which of the standard options do you recommend and why?
    Why: Guideline options include: Standard doublet chemotherapy with bevacizumab; anti-EGFR antibodies are less effective in HER2-amplified tumours; tucatinib-trastuzumab-FOLFOX is under test in MOUNTAINEER-03.
  7. Am I a candidate for FOLFOX (5-FU, leucovorin, oxaliplatin), FOLFIRI (5-FU, leucovorin, irinotecan), Bevacizumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  8. How do the results of A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.