BREAKING BRAF
SUPPORTING > INFORMING > CAMPAIGNING
Treating BRAF
MSI-High
Although different Oncologists favour slightly different drugs and regimens, the guide below is the generally accepted pathway for the treatment of BRAF MSI-High for most NHS patients. This may differ if you have additional gene mutations, or have additional medical issues.
There are additional private drug and diagnostic options available and we have indicated where optional drugs are private prescription (such as Bevacizumab/Avastin at First Line Chemotherapy).
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This guide doesn't include trial drugs or yet-to-be-licensed drugs.
Surgery
Depending upon the size and location of your tumour/s, and any potential blockages caused by these, you may or may not have surgery before commencing treatment - see section below for how and why such decisions are made.
Neoadjuvant or
Adjuvant
Chemotherapy?
These terms simply indicate whether you have chemotherapy (first line treatment) before or after surgery.
Neoadjuvant treatment helps to shrink the tumour/s as much as possible, before surgery, to improve results.
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Adjuvant treatment happens after surgery. This chemotherapy happens after surgery because:
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You were admitted as an emergency with a bowel blockage and operated on before finding out that you had bowel cancer
OR
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2. You were admitted for surgery soon after diagnosis because your tumour was blocking, or about to block, your bowel and cause complications.
First Line Treatment: Chemotherapy
Although NICE guidelines allow for MSI-High BRAF-mutated metastatic (Stage 4) bowel cancer to be treated with first line Immunotherapy (Ipilimumab and Nivolumab combined, as of 28 May 2025), our patient group shows us that it is common for peoplel to not know that they have a BRAF mutation at the very start of their treatment.
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So, unless you have had histology that shows you are BRAF MSI-High and you are Stage 4, you can expect to start on either a 5-Fluorouracil (5FU) or Capecitabine based treatment. This might also include Oxaliplatin, Irinotecan and – if you’re paying for it alongside NHS treatment, or a private healthcare patient – Bevacizumab (primary brand name: Avastin). You’ll see terms such as CAPOX, FOLFOX, FOLFOXIRI, FOLFIRI, etc. This is a way of notating the various medicines that comprise your treatment.
For example, FOLFOXIRI is FOLF (5FU) + OX (Oxalaplatin) + IRI (Irinotecan).
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Your Oncologist will decide what dosage to give you and this may change through your treatment, based on your health, blood results, other mutations, your response and your side effects. It is really important you keep a record and tell your team about any side effects you experience, as they may be able to reduce the dose and improve your tolerance.
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If you have been lucky enough to have received Biomarker testing prior to your first line of treatment and your cancer has metastasised, your first line treatment will now usually be Ipilimumab and Nivolumab (was Pembrolizumab before 28 May 2025).
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There are exceptions to this - it depends upon your cancer, your progression, where your metastases are located and other medical and mutation factors that your Oncologist will take into account. Your Oncologist is the best person to speak to about your individual medical situation.
Second Line Treatment: Immunotherapy
It is always worth pushing for biomarker testing and hopefully by Second Line treatment, you will have a diagnosis of BRAF MSI-High and/or Deficient Mismatch Repair gene (d/MMR).
The standard Second Line treatment for BRAF MSI-High is Immunotherapy. BRAF MSI-High has been shown to respond very well to immunotherapy drugs.
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For most patients, including those who had Chemotherapy previously, this will be Ipilimumab and Nivolumab (approved 28 May 2025 - was previously Pembrolizumab).
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Some BRAF MSI-High patients have been able to achieve long and even permanent periods of NED (No Evidence of Disease) at this stage with these drugs.
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There are exceptions to this - it depends upon your cancer, your progression, where your metastases are located and other medical and mutation factors that your Oncologist will take into account. Your Oncologist is the best person to speak to about your individual medical situation.
Third Line
Treatments and Beyond
A number of BRAF MSI-High patients exhibit a resistance to the standard second line immunotherapy drugs.
If you have tried immunotherapy and it hasn't worked for you, your Oncologist may opt to do a Chemotherapy re-challenge at this point. Depending on your level of resistance exhibited, you may or may not have an immunotherapy drug added in to your chemotherapy, to try and persuade your cancer to respond to immunotherapy drugs.
You may have been recommended to participate in a drug trial, or you may be given Lonsurf (Trifluridine Tipiracil) with Bevacizumab (also known as Avastin). You may be offered a drug called Regorafenib or you may be considered for treatment with Panitumumab with or without Bevacizumab (Avastin).
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You may want to get a second opinion, at this stage so you know all of your options, before deciding what to do next. See our section 'Second Opinions' for details of how to get one.
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There are exceptions to this - it depends upon your cancer, your progression, where your metastases are located and other medical and mutation factors that your Oncologist will take into account. Your Oncologist is the best person to speak to about your individual medical situation.