Abemaciclib

Abemaciclib (Verzenio) 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.

The first available CDK 4/6 inhibitor, palbociclib (Ibrance), was approved by the FDA in 2015. Another, ribociclib (Kisqali), was approved in early 2017. Later that year, abemaciclib became the third medicine of this type to be approved for hormone receptor-positive, HER2-negative metastatic breast cancer. In 2021, the FDA expanded the approval of abemaciclib for use in high-risk, early-stage breast cancer. It is the only CDK 4/6 inhibitor approved for use in early-stage breast cancer.

While these three medicines mostly work in the same way, abemaciclib differs slightly from the other two in its dosing. Abemaciclib is taken continuously, whereas palbociclib and ribociclib are given in cycles with breaks.

How abemaciclib works

Cyclin-dependent kinases 4 and 6 are two proteins that help some breast cancers to grow. Medicines like abemaciclib 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 abemaciclib

Abemaciclib is FDA approved to treat both high-risk, early-stage breast cancer and metastatic breast cancer. It can be taken by postmenopausal women, women who who are peri- or premenopausal, and men, although recommendations for these groups can vary.

Abemaciclib in early-stage breast cancer

Abemaciclib is FDA approved to treat high-risk, early-stage breast cancer that is hormone-receptor positive, HER2-negative, and node-positive. Determining whether a cancer is at high risk for recurrence depends on different features of the cancer. This includes the number of lymph nodes that have cancer and the size and grade of the cancer.

When used in high-risk early-stage breast cancer, abemaciclib is given with tamoxifen or an aromatase inhibitor after the primary treatment (often surgery).

In October 2023, five-year outcomes from analysis of the abemaciclib monarchE study were released. This study follows two groups of people diagnosed with hormone receptor-positive, HER2-negative, lymph-node-positive early-stage breast cancer:

• One group (2,808 people) took abemaciclib and endocrine therapy for two years after surgery.
• The other group (2,829 people) took endocrine therapy alone.

Both groups continued the endocrine therapy for at least five years. Here is what the five-year analysis found:

Reducing the risk of any recurrence (local or distant): In early-stage hormone receptor-positive, HER2-negative, node-positive breast cancer, adding abemaciclib reduced the risk of local or distant recurrence by 32% compared with endocrine therapy alone. Five-year invasive disease-free survival rates were:

• 83.6% in the group taking endocrine therapy plus abemaciclib
• 76% in the group taking endocrine therapy alone

The absolute increase in disease-free survival was 7.6%.

Reducing the risk of distant recurrence: Adding abemaciclib to endocrine therapy reduced the risk of distant recurrence by 32.5%. Five-year distant relapse-free survival rates were:

• 86% in the group taking endocrine therapy plus abemaciclib
• 79.2% in the group taking endocrine therapy alone

The absolute increase in distant relapse-free survival was 6.7%.

In high-risk early-stage breast cancer, pre- and perimenopausal women, as well as men, need to take a luteinizing hormone-releasing hormone (LHRH) agonist, such as goserelin (Zoladex), when taking abemaciclib and an aromatase inhibitor. LHRH agonists suppress hormone production in the body.

“When deciding on the combination of abemaciclib with tamoxifen or aromatase inhibitor in a premenopausal patient, the side effect profile of the two should be considered,” Dr. Avery says. “A premenopausal patient could be treated with agents to induce menopause in combination with aromatase inhibitor, or with tamoxifen alone. Data for other studies suggest that outcomes may be better with induction of menopause in higher-risk patients.”

It's important to know that when abemaciclib was originally approved to treat early-stage breast cancer, eligibility required testing to confirm that the cancer had a certain level of the protein Ki-67, an indicator of how rapidly cancer cells divide and grow. In March 2023, the Ki-67 testing requirement was removed, opening eligibility to more people. If you’re considering abemaciclib and someone tells you that you need Ki-67 testing, let them know that it’s no longer required. You can also direct them to the March 2023 FDA abemaciclib update for more information.

Abemaciclib in metastatic breast cancer

Abemaciclib is FDA approved for three uses in people with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer:

• It is given with an aromatase inhibitor as the first treatment for advanced or metastatic breast cancer.
• It is given with fulvestrant (Faslodex) to treat advanced or metastatic breast cancer that has progressed after taking hormonal therapy.
• It is given alone to treat advanced or metastatic breast cancer that has progressed after treatment with hormonal therapy and chemotherapy.

Pre- and perimenopausal women need to take a luteinizing hormone-releasing hormone (LHRH) agonist, such as goserelin, to suppress hormone production in the body if they are taking abemaciclib plus an aromatase inhibitor or fulvestrant for advanced or metastatic breast cancer.

Men taking abemaciclib plus an aromatase inhibitor for advanced or metastatic breast cancer also need to take an LHRH agonist to suppress hormone production.

Abemaciclib was FDA approved for these uses on the basis of several clinical trials:

• monarchE: Compared abemaciclib plus tamoxifen or an aromatase inhibitor, versus hormonal therapy alone, in people with lymph node-positive early-stage breast cancer at high risk of recurrence
• MONARCH3: Compared abemaciclib plus an aromatase inhibitor (anastrozole or letrozole) to an AI alone in postmenopausal women with metastatic breast cancer
• MONARCH2: Compared abemaciclib plus fulvestrant to fulvestrant alone in women with cancer that had grown during past hormonal therapy
• MONARCH1: Assessed abemaciclib alone in people with metastatic breast cancer that continued to grow on previous therapies

How abemaciclib is given

Abemaciclib is a pill, usually taken twice a day. The recommended dose depends on whether you are taking it alone, with an aromatase inhibitor, with tamoxifen, or with fulvestrant.

Unlike other CDK 4/6 inhibitors, which are taken in cycles with regular breaks, abemaciclib is taken every day through treatment. People with early-stage disease can take abemaciclib for two years. They may stop taking it sooner if the cancer comes back or the side effects are too severe. When given for metastatic breast cancer, abemaciclib may be taken on an ongoing basis for as long as it controls the cancer and side effects are manageable.

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

Side effects & things to remember

The most common side effect for abemaciclib is diarrhea. In a clinical trial, more than 80 percent of participants had diarrhea, but most cases were controlled with anti-diarrheal medicines and lowering the dose, if necessary. Let your doctor know right away if you notice loose stools so that you can begin preventive treatment.

Abemaciclib also may cause neutropenia, a low white blood cell count that makes infection more likely. Your doctor will watch your blood counts closely, especially during the first two months on the treatment. Other side effects reported in clinical trials of this medication included:

• Low red blood cell count, which can lead to fatigue
• Low blood platelet count, which can cause abnormal bleeding
• Nausea and vomiting
• Abdominal pain
• Small sores or ulcers in the mouth or on the lips
• Fatigue
• Headache
• Low appetite
• Hair loss
• Itching
• Swelling in the limbs

Tell your doctor about any medicines, supplements, or remedies you are taking before starting abemaciclib. Avoid eating grapefruit and any food or drinks that have grapefruit in them while taking this medicine.

Tell your doctor if you are pregnant, breastfeeding, or planning to do either. Abemaciclib may be dangerous to a fetus so it is recommended that you not take this medicine while pregnant and not get pregnant until at least 3 weeks after you have stopped treatment. It is not known if abemaciclib is transferred through breast milk. For this reason, do not breastfeed while taking abemaciclib or for 3 weeks after you stop.

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

Talk to your doctor about any side effects you experience and how to manage them. If you have a serious side effect, the dose may need to be lowered, or you may need to take a break from the medication. You can also visit our Side effects page to learn more.