CDK4/6 Inhibitors for Breast Cancer: How They Work, Side Effects and UK Availability

What are CDK4/6 inhibitors?

CDK4/6 inhibitors are a type of targeted cancer drug, sometimes called a cancer growth blocker. The name stands for cyclin-dependent kinase 4 and 6, which are two proteins inside cells that help cells grow and divide. According to Cancer Research UK, these drugs block those proteins, which slows down or stops the cancer cells from multiplying.

There are three CDK4/6 inhibitors used for breast cancer in the UK. They are palbociclib (brand name Ibrance), ribociclib (Kisqali) and abemaciclib (Verzenios). They are all taken as tablets or capsules at home, rather than given through a drip in hospital.

These drugs are used for breast cancer that is hormone receptor positive and HER2 negative. Hormone receptor positive means the cancer cells grow in response to the hormones oestrogen or progesterone. Because of this, CDK4/6 inhibitors are almost always given together with hormone (endocrine) therapy, not on their own. The two treatments work in different ways and are more effective as a pair.

This page is general information, not personal medical advice. Treatment choices depend on your particular cancer, your other health conditions and your wishes. Your oncologist, breast care nurse and GP know your own situation, so please always check with your treatment team about what is right for you.

How CDK4/6 inhibitors work

Healthy cells grow and divide in a careful, controlled way. Cancer cells have lost some of that control, so they keep dividing when they should not. In hormone-receptor-positive breast cancer, the proteins CDK4 and CDK6 act a bit like an accelerator pedal, pushing cells to keep dividing.

CDK4/6 inhibitors work by blocking these two proteins. According to Cancer Research UK, this stops the cancer cells from moving through their growth cycle, so they cannot divide and the cancer is slowed down. The aim is to keep the cancer under control for as long as possible.

Hormone therapy works differently. It lowers the amount of oestrogen in the body, or stops oestrogen reaching the cancer cells, which removes another signal telling the cancer to grow. Using a CDK4/6 inhibitor and hormone therapy together tackles the cancer in two ways at once. Research has shown this combination can keep the cancer from growing for longer than hormone therapy alone.

Who might be offered them

CDK4/6 inhibitors are mainly used for advanced (secondary or metastatic) breast cancer that is hormone receptor positive and HER2 negative. This means the cancer has spread beyond the breast, for example to the bones, liver or lungs. The NHS explains that secondary breast cancer cannot usually be cured, but treatments like these can control it well, often for a long time, while keeping side effects manageable.

For this type of advanced breast cancer, a CDK4/6 inhibitor combined with hormone therapy is often one of the first treatments offered. NICE, the body that decides which treatments the NHS funds, has recommended all three drugs in different situations:

• As a first treatment for advanced disease, a CDK4/6 inhibitor is usually combined with an aromatase inhibitor (a type of hormone therapy such as letrozole, anastrozole or exemestane).
• If the cancer has progressed after earlier hormone therapy, NICE has recommended palbociclib, ribociclib and abemaciclib each combined with fulvestrant, another type of hormone therapy given by injection.
• Some people may be offered a CDK4/6 inhibitor after earlier treatment, depending on what they have already had.

More recently, one CDK4/6 inhibitor has also been approved for some people with early breast cancer, to lower the risk of it coming back after surgery. We cover this in the next section. Whether any of these drugs is right for you depends on the exact features of your cancer, so your oncologist is the best person to advise you.

Use in early breast cancer to prevent recurrence

For most of their history, CDK4/6 inhibitors were used only for advanced breast cancer. That has started to change. In 2022, NICE recommended abemaciclib, alongside hormone therapy, on the NHS in England for some people with early breast cancer (NICE guidance TA810). It is given after surgery to help reduce the risk of the cancer returning.

This option is for a specific group: people with hormone-receptor-positive, HER2-negative early breast cancer that has spread to the lymph nodes and is judged to be at high risk of coming back. It is taken for a set period (in trials, up to two years) alongside hormone therapy, which is usually continued for several years in total. The aim here is different from advanced disease: rather than controlling cancer that has already spread, it is used to lower the chance of cancer returning after the main treatment.

Not everyone with early breast cancer needs or is suitable for this treatment. Your oncologist will look at the size and grade of the cancer, how many lymph nodes are affected and other features to work out whether it could help you. If you would like to know whether you might be eligible, this is a good question to raise with your treatment team.

How they are taken and how treatment is monitored

All three drugs are taken at home as tablets or capsules. The exact schedule differs between them, and your team will give you clear written instructions. According to Cancer Research UK, palbociclib and ribociclib are usually taken once a day for 21 days, followed by a 7-day break, in a 28-day cycle. Abemaciclib is usually taken twice a day, every day, without a break.

Because these drugs can affect the blood and other parts of the body, you will have regular check-ups and blood tests while taking them. This monitoring is a normal part of treatment and helps your team keep you safe. Depending on the drug, this can include:

• Regular blood tests to check your white blood cells, especially in the first few months. A drop in a type of white cell called neutrophils (neutropenia) is common with these drugs and is usually managed by pausing treatment or lowering the dose.
• Blood tests to check how well your liver is working.
• For ribociclib, heart tracing tests called ECGs, because it can occasionally affect the heart's rhythm (a change called QT prolongation). Your team will check this before and during early treatment.
• Regular reviews of how you are feeling and any side effects, so the dose can be adjusted if needed.

If side effects build up, your team may pause the drug for a short time or reduce the dose. This is common and does not usually mean the treatment has stopped working. Take the tablets exactly as prescribed, do not stop suddenly without advice, and tell your team about any new symptoms. Always check before starting any new medicines, including ones bought from a pharmacy, as some can interact with these drugs.

Side effects to know about

Like all cancer treatments, CDK4/6 inhibitors can cause side effects, and these vary from person to person and between the three drugs. Many side effects can be managed well, especially when reported early. Cancer Research UK and Macmillan Cancer Support list the more common ones, which include:

• A drop in white blood cells (neutropenia), which can raise the risk of infection. This is one of the most common side effects, particularly with palbociclib and ribociclib.
• Tiredness (fatigue), which can be significant and may build up over time.
• Feeling sick (nausea) and, less often, being sick.
• Diarrhoea, which is especially common with abemaciclib and is usually managed with anti-diarrhoea medicine, drinking plenty of fluids and dose adjustments.
• A low red blood cell count (anaemia), which can add to tiredness and breathlessness.
• Hair thinning, mouth soreness, headache, joint or muscle aches and a reduced appetite.

Because neutropenia can increase the risk of infection, it is important to know the signs of infection. The NHS advises contacting your treatment team's 24-hour advice line straight away if you have a high temperature, feel shivery or unwell, or have any other signs of infection, as this can need urgent treatment.

Less commonly, these drugs can affect the lungs, causing inflammation (pneumonitis or interstitial lung disease). The UK medicines regulator, the MHRA, advises seeking medical advice quickly if you develop new or worsening breathlessness, a cough or other breathing problems. Ribociclib can occasionally affect the heart's rhythm, which is why ECG monitoring is used. Your team will explain the specific things to watch for with your drug and give you a number to call.

This is not a full list, and most people do not get every side effect. The patient information leaflet that comes with your medicine has the complete details, and your breast care nurse or pharmacist can talk you through what to expect and how to cope.

Availability on the NHS

All three CDK4/6 inhibitors are available on the NHS where NICE has recommended them and a person meets the criteria. NICE has approved palbociclib, ribociclib and abemaciclib for hormone-receptor-positive, HER2-negative advanced breast cancer in different combinations, and abemaciclib for some people with high-risk early breast cancer. NHS care is free at the point of use, so eligible patients in the UK do not pay for these drugs themselves.

Arrangements can differ slightly between England, Scotland, Wales and Northern Ireland, as each nation has its own process for approving NHS medicines (for example the Scottish Medicines Consortium in Scotland). Your oncologist will know what is available where you live and which drug is most suitable for your cancer. If you are ever unsure whether a treatment is an option for you, it is fine to ask your team directly.

Even where effective treatments exist, people can only benefit if their cancer is found in time and they can get the care they need. Finding breast cancer earlier widens the range of treatments that may help. As a charity, our work focuses on raising awareness, encouraging early detection and supporting fair access to diagnosis and treatment, so that more people are found earlier and can benefit from the treatments available.