CDK4/6 inhibitors are a newer class of medicines used to treat certain types of metastatic breast cancer, which is cancer that has spread to other parts of the body, such as the bones or liver. These medicines interrupt the process through which breast cancer cells divide and multiply. To do this, they target specific proteins known as the cyclin-dependent kinases 4 and 6, abbreviated as CDK4/6. That's why you may hear them referred to as “targeted therapies.”
Currently there are three CDK4/6 inhibitors used to treat metastatic breast cancer:
- Ibrance (chemical name: palbociclib)
- Kisqali (chemical name: ribociclib)
- Verzenio (chemical name: abemaciclib)
Read on to learn more about:
- How CDK4/6 inhibitors work
- Choosing a CDK4/6 inhibitor
- Side effects of CDK4/6 inhibitors
- Switching between CDK4/6 inhibitors
How do CDK4/6 inhibitors work?
The CDK4/6 proteins, found both in healthy cells and cancer cells, control how quickly cells grow and divide. In metastatic breast cancer, these proteins can become overactive and cause the cells to grow and divide uncontrollably. CDK4/6 inhibitors interrupt these proteins in order to slow or even stop the cancer cells from growing.
CDK4/6 inhibitors are used to treat metastatic breast cancers that are hormone-receptor-positive and HER2-negative. When a cancer is hormone-receptor-positive, this means that its growth is fueled by the hormones estrogen, progesterone, or both. HER2-negative cancers have tested negative for a protein called human epidermal growth factor receptor 2, or HER2, which promotes cancer cell growth. Therefore, HER2-negative cancers are not eligible for treatments that target the HER2 protein (such as Herceptin). More than two out of every three breast cancers are both hormone-receptor-positive and HER2-negative.1
All three CDK4/6 inhibitors are pills taken by mouth, but they are used a little bit differently. Verzenio is a pill that you take every day, either alone or with other treatments. It appears to affect the CDK4 protein more than the CDK6 protein. Ibrance and Kisqali affect both CDK4 and CDK6 and have to be taken along with hormonal therapy. They are also given in 4-week cycles that include a week-long break — so you would take the medication for 3 weeks and then take 1 week off.
Choosing a CDK4/6 inhibitor: Which one is right for you?
Ibrance, Kisqali, and Verzenio have not been directly compared to each other in a clinical trial. Still, doctors consider them to work equally well. Your treatment team can help you decide which one is right for your situation. This may depend on factors such as:
- what treatments you have had in the past, if any
- how quickly the cancer progressed after previous treatment
- if you are a woman, whether you are premenopausal or postmenopausal
- the side effects associated with each CDK4/6 inhibitor
- whether you and/or your treatment team prefer that you take medication continuously, as you would with Verzenio, or on a 3-week on/ 1-week off cycle (Ibrance and Kisqali)
- whether your health insurance favors one of the medications over the others
Each CDK4/6 inhibitor is approved by the U.S. Food and Drug Administration (FDA) for use in different subgroups of patients with metastatic breast cancer that is both hormone-receptor-positive and HER2-negative. (If you live outside the U.S., not all of these CDK4/6 inhibitors may have been approved yet, so check with your doctor.) Keep in mind that these approvals are likely to change over time, as clinical trials are still ongoing to figure out if CDK4/6 inhibitors can benefit additional groups.
In selected cases, CDK4/6 inhibitors also may be used to treat locally advanced breast cancer, which is cancer that has spread to tissues near the breast but not to other parts of the body. Your doctor can help you decide if this makes sense for you.
Ibrance (chemical name: palbociclib)
- For postmenopausal women and men: Ibrance can be used in combination with an aromatase inhibitor to treat patients who have not had hormonal therapy before. Aromatase inhibitors, which are a type of hormonal therapy, include Arimidex (chemical name: anastrozole), Aromasin (chemical name: exemestane), and Femara (chemical name: letrozole).
- For all women and men: Ibrance can be used in combination with the hormonal therapy Faslodex (chemical name: fulvestrant) to treat cancer that has grown after previous hormonal therapy. Premenopausal and perimenopausal women who take Ibrance in combination with Faslodex also should be treated with a medicine to suppress ovarian function.
Kisqali (chemical name: ribociclib)
- For premenopausal, perimenopausal, or postmenopausal women: Kisqali can be used with an aromatase inhibitor, such as Arimidex, Aromasin, or Femara, to treat patients who have not had previous hormonal therapy. Premenopausal and perimenopausal women who take Kisqali also should be treated with a medicine to suppress ovarian function.
- For postmenopausal women: Kisqali can be used with Faslodex to treat patients who have not had hormonal therapy before, or whose cancer has progressed after previous treatment with another hormonal therapy.
Verzenio (chemical name: abemaciclib)
- For postmenopausal women: Verzenio is used in combination with an aromatase inhibitor (Arimidex, Aromasin, Femara) in patients who have not had hormonal therapy before.
- For all women: Verzenio can be used in combination with Faslodex if the cancer has progressed after previous hormonal therapy. Premenopausal and perimenopausal women who take Verzenio in combination with Faslodex also should be treated with a medicine to suppress ovarian function.
- For all women and men: Verzenio also is used by itself to treat women and men if the cancer progressed after hormonal therapy treatment and earlier chemotherapy for metastatic breast cancer. These are general guidelines for the use of CDK4/6 inhibitors. You and your treatment team can discuss the particulars of your situation and what makes the most sense for you.
Note that if you are pregnant or planning to get pregnant, you should not take any of the CDK4/6 inhibitors. These medications can harm the developing fetus. It is important to use effective birth control while you are taking a CDK4/6 inhibitor and for at least 3 weeks after your last dose. In addition, men who take the CDK4/6 inhibitor Ibrance are also advised to use contraception while on treatment and for 3 months after finishing the medication.
Side effects of CDK4/6 inhibitors
Like most cancer medicines, CDK4/6 inhibitors cause side effects, but they tend to be less intense than those caused by chemotherapy. The most common side effects of all three medicines are:
- low white blood cell counts (also called neutropenia)
- anemia (low red blood cell counts)
- low platelet counts
If you are taking a CDK4/6 inhibitor, your doctor will monitor your blood counts before and during treatment. Your doctor also will order liver function tests, since these medications can sometimes affect the liver. Testing will usually take place every 2 weeks until your treatment team sees how your body responds to the CDK4/6 inhibitor. Some dose adjustments may need to be made during that time. After the first 2 months of treatment, testing usually can occur less frequently.
Even though every patient is different, doctors have observed that certain side effects tend to be more pronounced with some CDK4/6 inhibitors than others — and this might influence treatment decisions.
Verzenio, for example, is associated with a significant risk of gastrointestinal (GI) issues. Diarrhea is common, and in about 10 percent of patients it can be severe, leading to dehydration or infection. For most people, it can be managed with an anti-diarrheal medicine such as Imodium (chemical name: loperamide), greater fluid intake, and changes in diet. In some cases, it may be necessary to lower the dose or take a break from treatment, at least for the first month or two. If you already have GI issues — such as irritable bowel syndrome, colitis, diverticulitis, or frequent diarrhea, among others — your treatment team may lean away from Verzenio toward one of the other two CDK4/6 inhibitors.
In rare cases, Kisqali can cause a heart problem known as QT interval prolongation. (The QT interval is a measurement made on an electrocardiogram, or EKG, which is used to record the electrical activity of the heart.) This can lead to a fast or irregular heartbeat, which may be life-threatening. Patients taking Kisqali need to have an EKG every couple of weeks during the first few cycles of treatment. If you already have a heart condition, your treatment team may prefer one of the other CDK4/6 inhibitors.
These are not all of the potential side effects of CDK4/6 inhibitors. For more detailed information, visit our in-depth pages on Ibrance, Kisqali, and Verzenio. Keep in mind that side effects can vary widely from person to person.
Switching between CDK4/6 inhibitors
Although Ibrance, Kisqali, and Verzenio have not been directly compared to each other in a clinical trial, doctors consider them to work equally well. So if you are on one CDK4/6 inhibitor and experience serious side effects over time, even after adjusting the dosage, you and your doctor can talk about switching you to a different one. In most cases, though, your doctor should be able to find a dose that improves your side effects while maintaining the medication’s benefits.
If you switch to a different CDK4/6 inhibitor, there will usually be a period of time where you do not take the medicine while the new one is ordered. This also gives your body a chance to recover from the side effects.
If the cancer progresses while you are taking a CDK4/6 inhibitor, there is no evidence from medical studies to suggest that another CDK4/6 inhibitor will be effective. Your doctor may wish to change the hormonal therapy you are taking in combination with the medication. In certain cases, though, a doctor may decide it is worth trying a different CDK4/6 inhibitor. Your treatment team can advise you based on the particulars of your situation.
Written by: Kris Conner, contributing writer
Jennifer Armstrong, M.D., professional advisory board member
Brian Wojciechowski, M.D., medical adviser
- National Cancer Institute. Cancer Stat Facts: Female Breast Cancer Subtypes. 2019. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html
- Ibrance (palbociclib) prescribing information. Pfizer. New York, NY. 2018. Available at: http://labeling.pfizer.com/ShowLabeling.aspx?id=2191
- Kisqali (ribociclib) prescribing information. Novartis. East Hanover, NJ. 2018. Available at: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/kisqali.pdf
- Verzenio (abemaciclib) prescribing information. Eli Lilly and Company. Indianapolis, IN. 2018. Available at: http://pi.lilly.com/us/verzenio-uspi.pdf