What "RAS wild-type" means
The KRAS and NRAS genes are tested in every patient with metastatic colorectal cancer. If neither carries a mutation, the tumour is RAS wild-type: this is the case in just over half of patients. It matters because anti-EGFR antibodies, cetuximab and panitumumab, only work in these tumours. In RAS-mutated tumours they do not help and may even do harm.
Alongside RAS, BRAF is checked (with V600E, an anti-EGFR only makes sense together with encorafenib) and so is HER2 (if amplified, they work less well).
What these drugs do
EGFR is a receptor on the cell surface that gives the order to grow. Cetuximab and panitumumab are antibodies that block it from the outside. If the chain of command below it (RAS, BRAF) is intact, blocking the antenna slows the tumour; if RAS is mutated, the growth order fires on its own and blocking the antenna achieves nothing.
They are given intravenously in the day unit: panitumumab every 2 weeks, cetuximab every 1 or 2 weeks, together with chemotherapy (FOLFOX or FOLFIRI).
Why the side of the tumour matters
Tumours of the left colon (descending, sigmoid) and rectum are biologically different from those of the right colon (caecum, ascending). In studies, RAS wild-type patients with a left-sided tumour live longer with anti-EGFR + chemotherapy than with bevacizumab + chemotherapy (PARADIGM study, 2023). In the right colon the anti-EGFR benefit disappears or reverses, and guidelines prefer bevacizumab. That is why your oncologist will ask you, or check the report, where the primary tumour was.
Side effects and how they are managed
| Effect | What you will notice | What is done |
|---|---|---|
| Acne-like rash | Acne-type spots on the face, neck, chest and back from week 1-3; dryness, itching | Prevented from day one: moisturiser, sunscreen, sometimes oral doxycycline and a steroid cream. It usually improves over the weeks. In studies, having a rash is linked to a better response. |
| Nails and fingertips | Cracks on the fingertips, ingrown nails, inflammation around the nail (paronychia) | Wide shoes, do not cut nails too short, creams; report any infection. |
| Low magnesium | Cramps, tiredness, sometimes nothing | Checked at every blood test; replaced by mouth or intravenously. |
| Diarrhoea | Mainly when combined with irinotecan | Loperamide as prescribed; report if severe. |
| Infusion reaction | More with cetuximab, during the first doses | Premedication and monitoring in the day unit. |
How long, and what comes after
Treatment continues while it works and is tolerated. After several months a gentler maintenance phase is common (for example, fluoropyrimidine + anti-EGFR). If the tumour progresses, over time it acquires RAS resistance mutations; those mutations can disappear after months without anti-EGFR. That is why, after a treatment-free interval, the antibody is sometimes used again (rechallenge), first confirming with a blood liquid biopsy that RAS is still wild-type.
What to ask at your appointment
- Is my tumour RAS and BRAF wild-type? Has HER2 been checked too?
- Where was the primary tumour: right colon, left colon or rectum?
- Why anti-EGFR (or bevacizumab) in my case, and with which chemotherapy?
- What skin care should I start from day one, and whom do I call if it gets worse?
- If it stops working, would a rechallenge with liquid biopsy be considered later on?
