Pembrolizumab – a game-changer for head and neck cancer
If you have recently been diagnosed with a locally advanced head and neck squamous cell cancer and been told that you need surgery, I want to make sure you know about something before you go to theatre. There is a treatment available now that could meaningfully improve your chances of being cured, and it needs to be given before your operation, not after.
It is called pembrolizumab. Most patients, and most people in the field, simply call it Pembro. I have been giving it to patients since the original clinical trials, which means I have more experience with this treatment in head and neck cancer than almost any other clinician in the UK. Let me explain what it is, what it does, and why I think it matters so much.
What kind of cancer is Pembro for?
Pembro is for patients with locally advanced head and neck squamous cell carcinoma. In plain terms, that means cancers of the mouth, tongue, jaw, larynx (voice box) and lower throat, usually at stage 3 or 4, where the cancer may have spread to nearby lymph nodes in the neck.
These are generally HPV-negative cancers, which behave quite differently from the HPV-related throat cancers that are treated mainly with chemotherapy and radiotherapy. If you have been told that surgery is your primary treatment, with radiotherapy to follow, you are very likely in the group of patients who should be asking about Pembro.
How does it work?
Your immune system is remarkable. It patrols your body constantly, looking for threats including infections, damaged cells and cancer. The problem is that cancer cells are clever. They carry a surface marker called PD-L1 that acts rather like an invisibility cloak, sending a signal to your immune system that says: I’m a normal cell, nothing to see here. Your immune system is fooled, moves on, and the cancer is left to grow unchecked.
What Pembro does is strip that invisibility cloak away. It binds to the PD-L1 marker and blocks it, so that your immune system can finally see the cancer for what it is and attack it. It is not chemotherapy. It does not poison cells. It simply allows your own body to do what it was always designed to do.
What does the evidence show?
The results from the KEYNOTE-689 trial, published in the New England Journal of Medicine in June 2025, are genuinely exciting. This was a large international phase 3 trial, the gold standard of clinical evidence, involving 714 patients.
Patients who received Pembro alongside their standard treatment had a 60% event-free survival rate at three years, compared with 46% for those who had standard treatment alone. The risk of the cancer returning, progressing, or proving fatal was reduced by 30%. And perhaps most strikingly, the median time before any of those events occurred was nearly five years in the Pembro group, almost double the two and a half years seen in the standard treatment group.
These are not small gains. Leading oncologists are calling this the first genuinely positive trial result for this group of patients in twenty years, and I think that is absolutely the right way to describe it.
There is another benefit worth knowing about. Because Pembro starts working on the tumour before surgery, it can shrink the cancer before the operation. For some patients, this means that chemotherapy after surgery can be avoided altogether, with all the side effects that go with it. And having Pembro before surgery does not make the operation itself any more difficult or less likely to succeed.
Does it work for everyone?
Most patients in this group will be suitable. Your tumour needs to express the PD-L1 marker at a level called a combined positive score of 1 or above, which is tested on your biopsy sample as part of your standard diagnosis. Around 70% of patients in this group meet that threshold.
There are also a small number of patients with significant pre-existing autoimmune conditions, such as severe rheumatoid arthritis or polymyalgia, for whom stimulating the immune system further would not be appropriate. Your oncologist will go through your full medical history as part of the assessment.
What is the treatment actually like?
This is the part that tends to surprise patients most. Pembro is given as a straightforward outpatient treatment. You come in, we put up a drip, and the infusion takes a couple of hours. You are with us for half a day at most, then you go home. Three weeks later you come back for your second cycle. That is the pre-surgery phase done.
Most patients are able to carry on working during this time. The most common side effect is fatigue, because your immune system is being pushed to work very hard. In around one in ten patients, Pembro can trigger a mild autoimmune reaction, where the immune system becomes a little over-enthusiastic and reacts to healthy tissue such as the thyroid, lungs or bowel. These reactions are manageable and closely monitored, and the KEYNOTE-689 trial identified no new safety concerns.
After your surgery, you continue on Pembro for approximately one year alongside any radiotherapy your team recommends.
Is Pembro available now?
Yes. Pembro for this indication was approved by the FDA in the United States and by the European Commission in 2025, on the strength of the KEYNOTE-689 trial data. NICE, which approves treatments for NHS use in England, is completing its review, and approval is expected very shortly.
For patients with private health insurance, Pembro is already being accepted by insurers. It is evidence-based, fully licensed, and backed by the highest level of published clinical data.
For those considering self-funding, I want to be straightforward with you: this is a significant financial commitment. Each cycle costs £8,000, and the full course runs to approximately 15 cycles. That is a serious sum. But for many patients and their families, understanding what is at stake makes it a conversation worth having.
Why does the timing matter?
This is the most important thing I can tell you. Pembro has to be given before surgery. Once the operation has taken place, this particular window, and the survival benefit that comes with it, has passed.
Surgeons are rightly focused on getting patients into theatre, and that instinct is sound. But before you proceed, you need to know whether Pembro should come first. It is not a reason to delay indefinitely — the two pre-surgery cycles take six weeks in total — but it is absolutely a reason to seek an urgent opinion now, before decisions are made.
I have been involved with this treatment since the trials that led to its approval. That experience means I can assess your suitability quickly, review your PD-L1 results, and make sure that if Pembro is right for you, it is properly built into your treatment plan from the outset.
A second opinion at this stage is not disruptive. It could turn out to be the most important conversation you have.
For more information about Prof Nutting's work please visit the CV page, get in touch or arrange a consultation.