What Are Kinase Inhibitors?
Kinase inhibitors are a type of targeted therapy drug that may be part of the treatment for many kinds of cancer. In treating HR+ breast cancer, they block the action of certain proteins called kinases that send signals to cancer cells telling them to grow and spread.
How Do Kinase Inhibitors Work?
Kinases play an important role in helping cancer cells grow, spread, and stay alive. Some kinases have mutations that lead to out-of-control cell growth. Kinase inhibitors attach to certain targets on or inside cells to block the signal from the kinase.
Different drugs are designed to seek out different damaged proteins. With HR+ breast cancer, the most common targets are proteins called cyclin-dependent kinases 4 and 6 (CDK4/6). Others are the mTOR, PI3K and AKT.
Which Kinase Inhibitors Are Used to Treat HR+ Breast Cancer?
Kinase inhibitors that may be used to treat HR+ breast cancer include:
When Are Kinase Inhibitors Prescribed for HR+ Breast Cancer?
Whether your doctor recommends a kinase inhibitor will depend on several things, including the stage of the cancer, characteristics of the tumor, and your overall health.
They’re used most often to treat metastatic breast cancer. That’s cancer that has spread to other parts of your body. Your doctor may use the term stage IV or advanced breast cancer. Some kinase inhibitors are also approved to treat HR+ breast cancer at earlier stages.
Cancer cells taken during a biopsy are often tested to see if they have higher levels of certain proteins or have mutations to the genes that control them.
Under certain circumstances, it can be part of the treatment you start with. In other cases, you’ll only get one of these drugs if other treatments don’t work. You usually take them in combination with endocrine (hormone) therapy to make those drugs work better.
CDK4/6 inhibitors
Abemaciclib, palbociclib, and ribociclib are first-line treatment options (meaning a treatment you start with) for stage IV HR+ breast cancer in combination with endocrine therapy. They may also be used as a second-line add-on treatment if the cancer has progressed while you’ve been taking endocrine therapy.
Abemaciclib is also approved to treat earlier stages of HR+ breast cancer after surgery in combination with endocrine therapy if the cancer has spread to nearby lymph nodes and is likely to come back.
If you aren’t already in menopause, you must either take medication to stop your body from making estrogen while you’re taking a CDK4/6 inhibitor or have your ovaries removed.
mTOR inhibitors
Everolimus is a second-line treatment for stage IV HR+ breast cancer in combination with endocrine therapy for people who’ve gone through menopause. It might be added on if the cancer progresses either while you’re already taking an endocrine therapy medication or shortly after you stop.
PI3K inhibitors
Alpelisib is used as a second-line, add-on treatment for stage IV HR+ breast cancer in combination with endocrine therapy. You might get it if the tumor cells are positive for a mutation in the PIK3CA gene and the cancer progresses either during treatment with an endocrine therapy drug or after you stop taking one.
AKT inhibitors
Capivasertib can be used if the tumor cells have mutations in either the PIK3CA, AKT1, or PTEN genes because of the way those proteins work together to send growth signals to the cancer cells. It’s a second-line treatment you might get for stage IV HR+ breast cancer that progresses either while you’re taking an endocrine therapy drug or soon after you stop taking one.
How Do You Take Kinase Inhibitors?
Kinase inhibitors are pills – either capsules or tablets – that you take by mouth. How often you take them depends on the drug and your particular prescription. Your doctor will figure out the dosage you need based on a variety of things including whether you're taking the kinase inhibitor by itself or with another therapy. You might also have your dosage adjusted if you have side effects.
Some kinase inhibitors need to be taken with food. With most of them, you should avoid grapefruit and grapefruit juice because it can increase the amount of the drug in your bloodstream.
How long do you take kinase inhibitors?
Kinase inhibitors are designed to be taken long-term for stage IV HR+ breast cancer, as long as they keep working and the side effects are manageable.
If you’re taking abemaciclib for an earlier stage of cancer, the standard length of treatment is 2 years, unless the cancer comes back, or you can no longer tolerate the side effects.
How Effective Are Kinase Inhibitors?
Kinase inhibitors are most commonly used for HR+ breast cancer that is advanced and more difficult to treat. But combined with endocrine therapy, they can keep it from getting worse for many months. Some clinical trial studies found:
Are Kinase Inhibitors Safe?
Most people can take kinase inhibitors safely. There may be a risk for some serious side effects. These include:
- Lung inflammation
- Liver damage
- Low levels of blood cells
- Severe diarrhea
- Serious skin reactions
- Harm to a fetus
Abemaciclib may also cause blood clots.
A heart rhythm problem called a prolonged QT interval can happen with ribociclib.
What Are the Common Side Effects of Kinase Inhibitors?
Each of the kinase inhibitors comes with its own list of potential side effects. Some of the most common are:
- Diarrhea
- Fatigue
- Nausea and vomiting
- Headache
- Rash
- Mouth sores
- Hair loss
Kinase inhibitors can lower your amount of both red and white blood cells, which can cause anemia and make you more likely to get an infection.
Talk to your doctor about any side effects you’re having. They may be able to lower your dose to help manage them or give you other medications to help.
It’s important to get your diarrhea under control so it doesn’t lead to other problems like dehydration. There are both over-the-counter and prescription medicines you can take. Changes to your diet can also help, like cutting out spicy, fatty, or acidic foods. Be sure to drink plenty of water.
Who Should Not Take Kinase Inhibitors?
People who are pregnant should not take kinase inhibitors. They can be dangerous to a fetus. If you could become pregnant, talk to your doctor about using birth control while you’re taking them.
If you have liver, lung, or heart problems, you may be at higher risk for dangerous side effects.
How Much Do Kinase Inhibitors Cost?
Kinase inhibitors can be very expensive. The list price of CDK4/6 inhibitors is around $15,000 a month. Other kinds of these drugs cost $20,000 or more a month. For most of them, there are no generic versions available.
If you have insurance through your job or have a Medicare Part D plan, kinase inhibitors are often covered. In that case, you may only have a small out-of-pocket cost. You may have to get approval from your insurance company before you start one of these drugs, or you may have to try a different kind of treatment first to qualify for coverage.
Drug companies often have programs to lower the cost for people who can’t afford these medications.
Clinical Trials of Kinase Inhibitors for HR+ Breast Cancer
Doctors are always looking for better ways to treat HR+ breast cancer. Clinical trials are an important part of the process of developing new medications.
A number of clinical trials involving kinase inhibitors are being conducted. Some are testing new drugs. Others are testing new ways to use existing drugs, for example, in combination with other medications.
You can help doctors learn more and possibly get access to cutting-edge treatment by taking part in a clinical trial. Your doctor can help you decide if one may be right for you, and may know of one taking place in your area. You can also search a government-run database of ongoing studies at clinicaltrials.gov.
Is a Kinase Inhibitor Right for Me?
Kinase inhibitors can be used to treat HR+ breast cancer, but they aren’t right for everyone. Your doctor can help you decide whether they should be part of your treatment plan. Here are the main things that go into that decision:
Cancer stage and tumor makeup. Kinase inhibitors are most often used for HR+ breast cancer that has metastasized, or spread to other parts of your body. Some of them are only helpful if the cancer cells have certain gene mutations or receptors for a particular kinase. You’ll need testing to see if one might be appropriate.
Quality of life. Kinase inhibitors can cause serious side effects, and even those that aren’t life-threatening can be very unpleasant. These may be more of a problem if you have other health problems. You’ll need to consider your overall health and how well you can tolerate any potential side effects.
Cost. The amount you’ll pay for treatment with a kinase inhibitor depends on what your particular health plan covers. With no insurance, these drugs can cost $15,000 a month and up.