Palbociclib

Palbociclib (Ibrance) is a targeted therapy approved by the Food and Drug Administration to treat hormone receptor-positive breast cancer. It is a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor, which means it targets two specific kinases, or proteins, that help tumor cells reproduce. Those kinases are CDK 4 and CDK 6.

Palbociclib was the first CDK 4/6 inhibitor to be approved by the FDA in 2015 to treat hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. Two others, ribociclib (Kisqali) and abemaciclib (Verzenio), were approved in 2017. These three medicines mostly work in the same way, although dosing schedules and side effects can vary.

Since palbociclib was approved, CDK 4/6 inhibitors have become the recommended first-line treatment for most people with advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. They are usually given in combination with hormonal therapy, such as an aromatase inhibitor or fulvestrant (Faslodex). Because palbociclib was approved first, doctors tend to prescribe it more frequently. However, in clinical trials, all three medicines have been shown to help people live longer without cancer growth—for several months to a year longer versus hormonal therapy alone.

If you are eligible for a CDK 4/6 inhibitor, your doctor can help you decide which one makes the most sense for your situation.

How palbociclib works

Cyclin-dependent kinases 4 and 6 are two proteins that help some breast cancers to grow. Medicines like palbociclib are called CDK 4/6 inhibitors because they block these proteins from signaling cancer cells to multiply, which helps slow the growth or spread of the cancer.

Who gets palbociclib

Palbociclib is approved for use in people with advanced or metastatic, hormone receptor-positive, HER2-negative breast cancer. It can be given with:

• An aromatase inhibitor as initial therapy
• Fulvestrant (Faslodex), a selective estrogen receptor downregulator (SERD), also known as an estrogen receptor antagonist (ERA), in people who've experienced breast cancer progression following hormonal therapy

Pre- or perimenopausal women taking palbociclib plus an aromatase inhibitor or fulvestrant also need to take a luteinizing hormone-releasing hormone (LHRH) agonist, such as goserelin (Zoladex). LHRH agonists suppress hormone production in the body.

If you are a man taking palbociclib plus an aromatase inhibitor, talk with your doctor about whether adding an LHRH agonist might be beneficial for you.

For the uses mentioned above, palbociclib’s approval was based on two major clinical trials:

• PALOMA-2: Compared palbociclib plus letrozole with letrozole alone in postmenopausal women
• PALOMA-3: Compared palbociclib plus fulvestrant with fulvestrant alone in pre- and postmenopausal women whose cancer had continued to grow on previous hormonal therapy

How palbociclib is given

Palbociclib is taken as a capsule with food, or as a tablet taken with or without food, once a day for 21 consecutive days, followed by 7 days off. You and your doctor will discuss how many times you should repeat this cycle. Usually, it can be taken on an ongoing basis for as long as it controls the cancer and side effects are manageable.

Aromatase inhibitors are also pills taken by mouth. Fulvestrant is given as an injection into the buttock: two shots every two weeks in the first month, and then two shots every four weeks.

Side effects & things to remember

As with any medicine, the side effects of palbociclib can vary from person to person, but the most common serious side effects include:

• Neutropenia (a decrease in white blood cells known as neutrophils), which increases risk of infection
• Leukopenia (a decrease in white blood cells overall), which also increases infection risk
• Anemia (low red blood cell counts), which can lead to dizziness, weakness, bleeding or bruising, or shortness of breath

Your doctor will watch your blood counts closely, especially during the first two months on the treatment. Your doctor may need to lower the dose or give you a break from treatment if your cell counts fall below a certain range. You can protect yourself from infection by avoiding crowded places and people who are sick, wearing a mask, and washing your hands frequently.

Some people also may experience side effects such as:

• Fatigue
• Nausea
• Sore mouth
• Abnormalities in liver function tests
• Diarrhea
• Hair thinning or hair loss
• Vomiting
• Rash
• Loss of appetite
• Lung inflammation that can be severe

Call your doctor right away if you have any signs of infection, such as fever or chills, or other symptoms such as shortness of breath or difficulty breathing, chest pain, vomiting, weakness, or unusual bleeding. Getting help promptly can prevent a side effect from getting worse.

Before starting palbociclib, be sure to tell your doctor about any medicines you are taking, including vitamins, herbal supplements, and over-the-counter medicines. Also tell your doctor if you have ever had liver or kidney disease. You should avoid grapefruit and grapefruit juice while you are taking this medicine.

You should avoid becoming pregnant while you are receiving palbociclib and for at least 2 weeks after taking the last dose. Tell your doctor right away if you become pregnant or may be pregnant while you are undergoing treatment.

If you’re a man, palbociclib may affect your fertility (ability to have a child). Talk to your doctor if this is a concern for you.

Your doctor, pharmacist, or nurse can help you manage your side effects. If you have a difficult side effect, your doctor may decide to lower the dose or give you a break from treatment. You can go to our section on Side effects for more information.