Ribociclib

Ribociclib (Kisqali) is a targeted therapy approved by the Food and Drug Administration to treat stage II, stage III, and advanced or metastatic hormone receptor-positive, HER2-negative breast cancer.

Ribociclib 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.

There are also two other CDK 4/6 inhibitors available: palbociclib (Ibrance) and abemaciclib (Verzenio). These medicines mostly work in the same way, although dosing schedules and side effects can vary.

Like the other CDK 4/6 inhibitors, ribociclib is given in combination with hormonal therapy, such as an aromatase inhibitor or fulvestrant (Faslodex).

If you are eligible for a CDK 4/6 inhibitor, your doctor can help you decide between ribociclib and the other medicines.

How ribociclib works

Cyclin-dependent kinase 4 and 6 are two enzymes that help tumor cells grow and multiply. By blocking the action of CDK 4 and 6, ribociclib interferes with signals that tell cancer cells to quickly reproduce. This helps slow or even stop the growth or spread of cancer cells.

Who gets ribociclib

Ribociclib is approved to treat:

• Stage II and III hormone receptor-positive, HER2-negative early breast cancer that has a high risk of recurrence. It is given after surgery along with an aromatase inhibitor.
• Advanced or metastatic, hormone receptor-positive, HER2-negative breast cancer. It can be given with:
  • An aromatase inhibitor as initial treatment
  • Fulvestrant, a selective estrogen receptor downregulator (SERD), also known as an estrogen receptor antagonist (ERA), as initial treatment or after the cancer has grown while being treated with hormonal therapy

Pre- or perimenopausal women or men taking ribociclib plus an aromatase inhibitor or fulvestrant need to take a gonadotropin-releasing hormone (GnRH) agonist with it. GnRH agonists suppress hormone production in the body.

In early (stage II and III) breast cancer, ribociclib’s FDA approval was based on the NATALEE clinical trial. This trial showed that ribociclib reduced the risk of recurrence by 25% when compared with hormonal therapy alone.

In advanced and metastatic breast cancer, ribociclib’s FDA approval was based on several clinical trials. These trials showed that ribociclib improved overall survival when compared with hormonal therapy alone. They include:

• MONALEESA-2: Compared ribociclib plus letrozole in postmenopausal women against letrozole alone
• MONALEESA-7: Compared ribociclib plus an aromatase inhibitor or tamoxifen (plus the GnRH agonist goserelin) in pre- and perimenopausal women, versus hormonal therapy alone
• MONALEESA-3: Compared ribociclib plus fulvestrant in postmenopausal women against fulvestrant alone
• COMPLEEMENT-1: Compared ribociclib plus letrozole against letrozole alone in postmenopausal women, premenopausal women, and men. The latter two groups also received goserelin or leuprolide (both GnRH agonists)

How ribociclib is given

Ribociclib is a pill. It is usually taken once a day for the first 21 days of a 28-day cycle. The pill can be taken with or without food, and should be taken at the same time each day, preferably in the morning.

Ribociclib may be given with an aromatase inhibitor, which is also a pill.

Ribociclib can be paired with any aromatase inhibitor. If your doctor recommends letrozole (Femara), a 28-day supply of the medicines can be sold together. This is called a Kisqali Femara Co-Pack. It requires one copay rather than two, and costs the same as ribociclib alone, according to Novartis, the company that makes both medicines. You can also get each medication separately.

Ribociclib can also be given with fulvestrant, which is given as an injection into the buttock. In the first month, fulvestrant is given as two shots every two weeks; after that it is given as two shots every four weeks.

How long to take ribociclib

For stage II and III early breast cancer with a high risk of recurrence, ribociclib can be taken for three years unless the breast cancer recurs or side effects become unmanageable.

For advanced or metastatic breast cancer, you and your doctor will discuss how long you should take ribociclib. Usually, it can be taken on an ongoing basis for as long as it controls the cancer and side effects are manageable.

Side effects & things to remember

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

• Neutropenia (decrease in white blood cells known as neutrophils), which increases risk of infection
• Leukopenia (decrease in white blood cells overall), which also increases infection risk
• Abnormal liver function tests

Your doctor will watch your blood counts, especially during the first two months on the treatment, and perform liver function tests. Your doctor may need to lower the dose or give you a break from treatment if blood tests indicate there is a problem. You can protect yourself from infection by avoiding crowded places and people who are sick, wearing a mask, and washing your hands frequently.

Other side effects that some people may experience include:

• Nausea
• Fatigue
• Diarrhea
• Vomiting
• Hair loss
• Headache
• Constipation
• Rash
• Cough

Ribociclib also has some rare but potentially serious side effects that you should be aware of. These can include:

• Inflammation of the lungs
• Severe skin reaction
• A heart rhythm problem known as QT prolongation
• Liver problems

Because of these side effects, your doctor will run tests on your heart and liver function before and during treatment with ribociclib.

Call your doctor right away if you have symptoms such as an irregular heartbeat, chest pain, shortness of breath or difficulty breathing, skin rash, or fatigue. Also be sure to report any signs of infection, such as fever or chills. Getting help right away can prevent a side effect from getting worse.

Before starting ribociclib, 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 disease or heart problems. You should avoid grapefruit and grapefruit juice while you are taking this medicine.

You should avoid becoming pregnant while you are receiving ribociclib 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, ribociclib 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 experience difficult side effects, your doctor may recommend lowering the dose or stopping the medication temporarily. You can go to our section on Side effects for more information.