The first 60 days: HER2-amplified colorectal cancer
A few bowel cancers make too much of the HER2 protein, the same target as in HER2-positive breast cancer. Two HER2 drugs together, tucatinib and trastuzumab, shrink about four in ten of these tumours after chemotherapy has failed, and the antibody-drug conjugate trastuzumab deruxtecan works even when other HER2 drugs have stopped. Below, week by week, is what OnCo's record of HER2-amplified colorectal cancer says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Trastuzumab deruxtecan (DESTINY-CRC02; tumour-agnostic approval for immunohistochemistry 3+), watching for pneumonitis.
Standard doublet chemotherapy with bevacizumab; anti-EGFR antibodies are less effective in HER2-amplified tumours; tucatinib-trastuzumab-FOLFOX is under test in MOUNTAINEER-03.
Tucatinib plus trastuzumab (MOUNTAINEER); trastuzumab plus pertuzumab or lapatinib where tucatinib is unavailable.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example HER2 immunohistochemistry 3+, or 2+ with in situ hybridisation amplification, ERBB2 copy number on tumour or circulating tumour DNA sequencing, RAS and BRAF wild-type status, Left-sided or rectal primary), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include HER2-amplified, RAS and BRAF wild-type, left-sided, HER2-amplified with RAS mutation, HER2 activating mutations without amplification.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Metastatic, RAS wild-type, previously treated
- For my situation (metastatic, ras wild-type, previously treated), which of the standard options do you recommend and why?Guideline options include: Tucatinib plus trastuzumab (MOUNTAINEER); trastuzumab plus pertuzumab or lapatinib where tucatinib is unavailable.
- Am I a candidate for Tucatinib, Trastuzumab, Pertuzumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of MOUNTAINEER & MOUNTAINEER-03 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
After HER2 antibodies, or with RAS mutation
- For my situation (after her2 antibodies, or with ras mutation), which of the standard options do you recommend and why?Guideline options include: Trastuzumab deruxtecan (DESTINY-CRC02; tumour-agnostic approval for immunohistochemistry 3+), watching for pneumonitis.
- Am I a candidate for Trastuzumab deruxtecan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of DESTINY-CRC02 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, first line
- For my situation (metastatic, first line), which of the standard options do you recommend and 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.
- Am I a candidate for FOLFOX (5-FU, leucovorin, oxaliplatin), FOLFIRI (5-FU, leucovorin, irinotecan), Bevacizumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- 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?Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer, Zanidatamab, A Phase 2 Study of Zanidatamab in Patients With HER2-expressing Tumors, TL938 and Trastuzumab for Patients With HER2-positive Metastatic Colorectal Cancer?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “No randomised evidence yet for HER2 blockade in first line”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “RAS co-mutation blunts dual HER2 blockade and the best option for those patients is unclear”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal CancerPhase 3 · recruiting · NCT05253651An Open-label Randomized Phase 3 Study of Tucatinib in Combination With Trastuzumab and mFOLFOX6 Versus mFOLFOX6 Given With or Without Either Cetuximab or Bevacizumab as First-line Treatment for Subjects With HER2+ Metastatic Colorectal Cancer
- A Clinical Study of SPH5030 Tablets in the Treatment of Her2-positive/Mutated Biliary Tract OR Colorectal Cancer Patients.Phase 2 · recruiting · NCT06434597A Multicenter, Open, Single-arm Phase II Clinical Study to Evaluate the Efficacy and Safety of SPH5030 Tablets in Subjects With Her2-positive/Mutated Biliary Tract OR Colorectal Cancer.
- A Phase 2 Study of Zanidatamab in Patients With HER2-expressing TumorsPhase 2 · recruiting · NCT06695845A Phase 2, Open-label, Multicenter Study to Evaluate Efficacy and Safety of Zanidatamab for the Treatment of Participants With Previously Treated HER2-expressing Solid Tumors (DiscovHER PAN-206)
- TL938 and Trastuzumab for Patients With HER2-positive Metastatic Colorectal CancerPhase 2 · recruiting · NCT06589830A Phase 2 Study to Evaluate TL938 Combined With Trastuzumab in Patients With HER2-positive Metastatic Colorectal Cancer
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- HER2-amplified colorectal cancer: the full pageA few bowel cancers make too much of the HER2 protein, the same target as in HER2-positive breast cancer. Two HER2 drugs together, tucatinib and trastuzumab, shrink about four in ten of these tumours after chemotherapy has failed, and the antibody-drug conjugate trastuzumab deruxtecan works even when other HER2 drugs have stopped.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Immunohistochemistry (IHC): Staining a tissue slice with antibodies so a protein shows up in colour under the microscope.
- Sidedness (left vs right colon): Where in the colon a tumour starts changes its biology and which drugs work.
- Tumour-agnostic (tissue-agnostic) approval: A tumour-agnostic approval lets a drug be used for any cancer carrying a specific molecular feature, regardless of where it started.
Every term links to the glossary.