Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
- Study type
- Clinical guideline
- Study name
- ESMO mCRC 2026
- Design
- Clinical guideline (ESMO Guidelines Committee)
- Sample size
- Not applicable (clinical guideline)
- Source
- Ann Oncol · 2026
In plain words
This new guideline from the European Society for Medical Oncology (ESMO) is about the diagnosis, treatment and follow-up of colorectal (bowel) cancer that has spread to other organs. One of its important messages is that molecular tests on the tumour (such as MSI, BRAF, HER2 and KRAS) determine the choice of the best treatment; for example, patients with MSI-H tumours benefit greatly from immunotherapy. The choice of treatment should always be made with the treating doctor, based on each patient's situation.
Key guideline recommendations
- I, A; ESMO-MCBS v2.0: 4
For patients with dMMR or MSI-H metastatic colorectal cancer, the combination of nivolumab and ipilimumab is recommended.
- I, A
If dual immune checkpoint inhibitor therapy is not feasible, pembrolizumab is recommended.
- Recommended (level of evidence not stated in the available sources)
In disease with a BRAF V600E mutation, FOLFOX with encorafenib and cetuximab is recommended in first line (FOLFIRI with encorafenib and cetuximab is also recommended).
- III, B; ESMO-MCBS v2.0: 3
For patients with HER2-positive disease (IHC 3+), regardless of RAS status, who have previously received fluoropyrimidines, oxaliplatin and irinotecan and/or anti-HER2 agents, trastuzumab deruxtecan can be recommended.
- III, B; ESMO-MCBS v2.0: 3
For HER2-positive, RAS wild-type disease previously treated with fluoropyrimidines, oxaliplatin and irinotecan, the combination of tucatinib and trastuzumab can be recommended.
- III, C
Alternative options include lapatinib–trastuzumab, pertuzumab–trastuzumab or zanidatamab.
- II, B; ESMO-MCBS v2.0: 1
For disease with a KRAS G12C mutation previously treated with fluoropyrimidines, oxaliplatin and irinotecan, the combination of panitumumab and sotorasib is recommended.
- Recommended (level of evidence not stated in the available sources)
In refractory disease, trifluridine–tipiracil with bevacizumab is the standard approach; regorafenib or fruquintinib are subsequent options.
Study population
Patients with metastatic colorectal cancer.
Endpoints
Not applicable (clinical guideline).
Safety and side effects
Not applicable (clinical guideline); the PubMed record has no abstract.
Clinical significance and place in guidelines
This guideline replaces the 2023 version of the ESMO guideline for metastatic colorectal cancer. Compared with the previous version, nivolumab-ipilimumab is now preferred in dMMR/MSI-H disease, and in disease with a BRAF V600E mutation, encorafenib-cetuximab with chemotherapy is recommended in first line.
Limitations
The PubMed record has no abstract, and the recommendations on this card were taken from secondary summaries of the full text; for the complete list of recommendations and levels of evidence, consult the full text of the guideline.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.