How does immunotherapy work for head and neck cancer?
If you or someone you love has been diagnosed with head and neck cancer, you may have questions about immunotherapy and whether it could be part of your treatment plan.
One immunotherapy drug used to treat certain head and neck cancers is pembrolizumab (Keytruda). It works differently from chemotherapy by helping your immune system recognize and attack cancer cells.
Pembrolizumab is a type of immunotherapy called an immune checkpoint inhibitor. It targets a protein called PD-1 on immune cells. Cancer cells can use this protein to hide from your immune system. Pembrolizumab blocks this interaction, helping your immune system recognize cancer cells and fight them.
Unlike chemotherapy, which directly attacks cancer cells, pembrolizumab works by changing how your immune system responds to cancer. This means side effects can also be different from chemotherapy.
When is pembrolizumab used for head and neck cancer?
Pembrolizumab is approved by the U.S. Food and Drug Administration (FDA) for several situations involving head and neck squamous cell carcinoma (HNSCC), the most common type of head and neck cancer.
Your treatment options depend on factors such as the stage of your cancer, whether it can be removed with surgery, whether it has returned or spread, and certain tumor biomarkers.
Pembrolizumab may be used:
- Before and after surgery for certain locally advanced cancers. In June 2025, the FDA approved pembrolizumab for adults with resectable, locally advanced HNSCC whose tumors test positive for PD-L1. Treatment begins before surgery and continues afterward alongside radiation, with or without chemotherapy, followed by pembrolizumab alone.
- As a first treatment for recurrent or metastatic cancer. Pembrolizumab may be given alone to patients whose tumors express PD-L1 or in combination with chemotherapy, depending on the treatment plan.
- After cancer progresses during or following platinum-based chemotherapy. Pembrolizumab may be used alone in certain patients whose cancer has returned or spread.
These approvals reflect how immunotherapy is increasingly being used at different stages of head and neck cancer treatment.
What is PD-L1, and why does it matter?
Your doctor may recommend testing your tumor for a protein called PD-L1 before deciding whether pembrolizumab is appropriate.
PD-L1 is a protein that cancer cells and other cells in the tumor environment may produce. It can interact with PD-1 on immune cells, helping cancer cells avoid an immune response.
A test called the combined positive score (CPS) measures PD-L1 expression in the tumor and certain surrounding immune cells.
For some head and neck cancers, a CPS of 1 or higher is needed for pembrolizumab to be used alone as a first-line treatment or in the perioperative setting.
However, pembrolizumab combined with chemotherapy may be an option for certain patients regardless of PD-L1 status.
Your doctor can explain what your biomarker results mean and how they affect your treatment options.
What can you expect when receiving pembrolizumab?
Pembrolizumab is usually given through an intravenous (IV) infusion, meaning the medication enters your bloodstream through a vein. The infusion itself typically takes about 30 minutes. Your appointment may take longer because your care team may check your symptoms, review blood tests, and monitor you before or after treatment.
Pembrolizumab may be given alone or alongside other treatments, such as chemotherapy or radiation.
How long will you receive treatment?
The length of treatment depends on your cancer type, stage, treatment setting, and response.
For recurrent or metastatic disease, treatment may continue until your cancer progresses, side effects become unacceptable, or you reach the planned treatment duration. When pembrolizumab is used before and after surgery, the treatment schedule is different and follows a planned sequence involving surgery and, when appropriate, radiation or chemotherapy.
Your care team will explain your schedule and whether treatment may be adjusted.
What are the side effects of pembrolizumab?
Because pembrolizumab activates your immune system, it can sometimes cause your immune system to attack healthy cells and organs.
Side effects vary from person to person. Some people experience mild symptoms, while others may develop more serious complications.
Common side effects
Possible side effects include:
- Fatigue or feeling unusually tired
- Skin rash or itching
- Diarrhea
- Nausea
- Cough
- Muscle or joint pain
- Decreased appetite
- Constipation
Some people also develop changes in thyroid function, which may cause symptoms such as fatigue, weight changes, or feeling unusually cold or warm.
If pembrolizumab is given with radiation or chemotherapy, you may experience additional side effects related to those treatments.
For example, radiation to the head and neck can cause mouth sores, dry mouth, difficulty swallowing, and skin irritation. These effects may overlap with symptoms caused by cancer or immunotherapy.
Serious immune-related side effects
Sometimes, pembrolizumab causes inflammation in healthy organs. These complications are called immune-related adverse events.
They can affect different parts of your body, including:
- Lungs: inflammation that may cause a new or worsening cough or shortness of breath
- Intestines: inflammation that may cause diarrhea or abdominal pain
- Liver: inflammation that may cause abnormal liver tests, sometimes without noticeable symptoms
- Thyroid and other hormone-producing glands: inflammation that may cause hormonal changes, fatigue, or changes in weight
- Kidneys: inflammation that may affect kidney function
- Skin: severe rash or blistering
Less commonly, inflammation can affect the heart, nervous system, or other organs.
These complications can sometimes be serious or life-threatening. They may develop during treatment or even after treatment has ended.
Contact your care team promptly if you notice new or worsening symptoms. Don’t wait until your next appointment to report them.
What questions should you ask your doctor?
Before starting pembrolizumab, consider asking:
- Is pembrolizumab appropriate for my type and stage of head and neck cancer?
- Has my tumor been tested for PD-L1?
- Will I receive immunotherapy alone or with chemotherapy, radiation, or surgery?
- How often will I receive treatment, and how long will it continue?
- What side effects should I watch for?
- Who should I contact if I experience symptoms between appointments?
- Could my other medications or health conditions affect treatment?
- What happens if pembrolizumab does not work for me?
Understanding your immunotherapy options
Pembrolizumab has expanded treatment options for certain people with head and neck cancer, including patients receiving treatment before and after surgery and those with recurrent or metastatic disease.
However, immunotherapy isn’t appropriate for everyone. Your treatment plan depends on your cancer’s characteristics, biomarker results, overall health, and previous treatments.
Understanding how pembrolizumab works, what side effects to watch for, and how your care team will monitor you can help you feel more prepared to discuss your treatment options.
You don’t have to navigate treatment decisions alone. Ask your oncologist questions, report new symptoms, and work with your care team to understand what each step of treatment means for you.
Disclaimer: The information provided in this article is for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Outcomes4Me is not acting as your caregiver, and any suggestions or guidance offered should not replace the advice of your healthcare provider or qualified medical professional. Always seek the guidance of your physician or other qualified health provider with any questions you may have regarding a medical condition.
