Your CDK4/6 Inhibitor Treatment Cycle for Metastatic Breast Cancer: A Practical Guide
CancerBreast Cancer

Your CDK4/6 Inhibitor Treatment Cycle for Metastatic Breast Cancer: A Practical Guide

Your CDK4/6 Inhibitor Treatment Cycle for Metastatic Breast Cancer: A Practical Guide
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Published on January 12, 2026
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CDK 4/6 inhibitors are a treatment for hormone receptor–positive (HR-positive), HER2-negative breast cancer that has spread to other parts of the body. They come as pills, and are often given with hormone therapy.

The dosing for some CDK4/6 inhibitors is different: They’re given on a three-week-on, one-week-off schedule that may be confusing at first.

Knowing what to expect during your treatment — including possible side effects and how to manage them — will help you feel more assured about taking CDK4/6 inhibitors for metastatic breast cancer.

CDK 4/6 Inhibitors

Cyclin-dependent kinases 4 and 6 (CDK 4/6) are proteins that allow cancer cells to divide uncontrollably. CDK inhibitors block these proteins to slow or stop breast cancer growth.

Three CDK4/6 inhibitors are approved to treat metastatic breast cancer:

  • palbociclib (Ibrance)
  • ribociclib (Kisqali)
  • abemaciclib (Verzenio)
Ibrance and Kisqali are given on a four-week cycle. Verzenio is different; you take it every day with no break.

Your doctor will check your blood at regular intervals during treatment. When you start taking these medications, your doctor may do blood tests once every two weeks. After the first couple of visits, the interval between blood tests will increase to once every four weeks — at the start of each treatment cycle.

Ibrance and Kisqali lower white blood cells the most. That's why they're given in a four-week cycle. You take the medicine for three weeks, followed by one week off. Every four weeks equals one cycle. After the cycle ends, you repeat it.

"That week of rest is so that you can rebuild your level of [white blood cells], so that you're able to fight off infections," says Rena Callahan, MD, a breast medical oncologist and associate clinical professor of medicine at UCLA Health.

Treatment Weeks 1 to 3: Managing Side Effects

During the first three weeks of the four-week cycle, you'll take Ibrance or Kisqali every day. You take Verzenio every day as well.

The following is the dosing schedule for each drug.

  • Ibrance: 125 milligrams (mg) (one pill) once a day for three weeks, then one week off

  • Kisqali: 600 mg (three pills) three times a day for three weeks, then one week off

  • Verzenio: 150 mg or 200 mg (one pill) twice every day

Like any other cancer drug, CDK 4/6 inhibitors have possible side effects, but there are things you can do to manage them. "We have the ability to decrease the dose if their initial dose is high, and give them supportive medication," says Neelam Desai, MD, a breast medical oncologist at Atrium Health Levine Cancer Institute in Matthews, North Carolina.

Neutropenia

Neutropenia is the name for a low white blood cell count, and it’s one of the most common side effects seen with CDK4/6 inhibitors — especially Ibrance and Kisqali. In a long-term safety analysis of three studies looking at Ibrance, more than 80 percent of participants who were taking Ibrance developed neutropenia.

 Studies of Kisqali found that neutropenia affected around 75 percent of people who took it.

Neutropenia may occur because these medications reduce many cells in your body that need CDK 4/6 proteins to divide, not just cancer cells. "These drugs can lower blood counts, including white blood cells, which are your infection-fighting blood cells," says Dr. Desai. CDK4/6 inhibitors also reduce the number of red blood cells that carry oxygen to your tissues (causing anemia), and platelets that help your blood clot, she says.

People with neutropenia are at higher risk for infections.

 The most common infections linked to CDK4/6 inhibitors are respiratory tract infections, urinary tract infections, colds, and gastroenteritis ("stomach flu"), says Dr. Callahan.

You don't have to live in a bubble, but do avoid close contact with anyone who is sick, says Callahan. Wash your hands often with warm water and soap. Watch for symptoms of infections and report them to your doctor.

"We generally tell our patients to call us if they have any signs of fever, congestion, cough, trouble breathing, burning during urination, increased frequency of urination, cloudy or foul-smelling urine, or diarrhea that's significant," Desai says.

Neutropenia will usually improve on its own within a few weeks. You'll get regular blood tests to check for this side effect. If you have severe neutropenia, your doctor can lower the CDK4/6 inhibitor dose, stop it temporarily, or delay the next cycle until your white blood cell count goes back up.

Fatigue

Tiredness is a possible side effect with all three drugs. Neutropenia and anemia are two of the main causes of fatigue. For severe fatigue you may need to talk to your oncologist about lowering the medication dose.

Mild fatigue is usually easy to manage on your own at home. "People who do some sort of exercise, even if it's a small amount but they do it consistently on most days, have a better chance of fighting the fatigue," Desai says. "Good nutrition helps, although it's not specifically going to increase blood counts."

A diet rich in these foods is helpful for fighting fatigue:

  • Colorful fruits and vegetables like oranges, berries, spinach, and broccoli
  • Whole grains like oats and brown rice
  • Omega-3 fats from oily fish like salmon, walnuts, and flaxseeds
  • Lean protein from chicken, beef, beans, or tofu

Diarrhea

Any of the CDK4/6 inhibitors can cause diarrhea, but especially Verzenio, says Desai. Up to 90 percent of people who take Verzenio get diarrhea, most within the first week of treatment.

The first treatment to try is an anti-diarrhea drug like Imodium. Drink more water and other fluids to prevent dehydration.

 A change in diet is also helpful. "The introduction of yogurt, probiotics, or banana flakes, and the avoidance of spicy, greasy, and heavy foods works really well," says Callahan.
Depending on how severe the diarrhea is, your doctor might lower the CDK4/6 inhibitor dose or ask you to stop taking the drug until this side effect resolves.

Liver Damage

Liver damage is a possible but rare side effect of Verzenio.

 Kisqali is more likely to harm the liver, as well as the bile ducts.

You'll have tests to check your liver function before you start taking Verzenio or Kisqali. Then you'll get tested every two weeks for the first two months on the medicine, and once a month after that. If you have abnormal results, your doctor might lower the dose, delay the next treatment cycle, pause the drug, or stop it altogether.

Lung Disease

Interstitial lung disease and pneumonitis can happen with any of the CDK4/6 inhibitors. These lung conditions are rare, affecting fewer than 1 percent of people who take these medicines, but they can be serious.

Tell your doctor right away if you have symptoms like shortness of breath or a cough. Imaging tests diagnose interstitial lung disease and pneumonitis. If you have lung disease, your doctor will have you pause the medicine right away. For severe pneumonitis or interstitial lung disease, you'll need to permanently stop taking the CDK4/6 inhibitor.

Prolonged QT Interval

The QT interval is how long it takes an electrical signal to travel through your heart's lower chambers and make it beat, then relax. Rarely, Kisqali prolongs the QT interval, which increases the risk for a life-threatening irregular heart rhythm.

"I don't consider this dangerous for the overwhelming majority of patients, but it does require monitoring of EKGs [electrocardiograms]," says Callahan. Your doctor will do a baseline EKG when you start taking Kisqali, repeat it in two weeks, and then as needed, says Desai. "Once you have determined that this [medicine] is not causing any issue with the electrical activity, then you don't need to check additional EKGs," says Callahan.

If you do develop a prolonged QT interval, stopping Kisqali should reverse this side effect.

Blood Clots

Between 2 percent and 5 percent of people who took Verzenio in studies developed blood clots such as deep vein thrombosis (DVT) and pulmonary embolism.

 Because a blood clot could be very serious, report symptoms like these to your doctor:
  • Swelling, pain, redness, or warmth in an arm or leg

  • Belly or side pain

  • Shortness of breath

  • Chest pain that gets worse when you exercise or take a breath

Treatment Week 4: Recovery

After three weeks on Ibrance or Kisqali, you'll get a week off. This is time for your neutrophils to regenerate. You'll still take hormone therapy every day during this week.

Use this time off to maximize your recovery and quality of life. Eat a nutritious diet. Take a daily walk or do other types of low-impact aerobic exercise. Sleep well. See a therapist or other mental health provider to talk about your emotional health. And do whatever fun activities you've been putting off because of your cancer treatment.

The Takeaway

  • CDK4/6 inhibitors for metastatic breast cancer come as a daily pill that you take together with hormone therapy.
  • These medicines can cause side effects like neutropenia, fatigue, and diarrhea.
  • Some side effects are manageable with diet, exercise, and other lifestyle changes.
  • For more severe side effects, your doctor might adjust your medicine dose or take you off the CDK4/6 inhibitor temporarily or permanently.

Resources We Trust

EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
Resources
  1. Conner K. What Are CDK4/6 Inhibitors? Breastcancer.org. January 13, 2025.
  2. Cancer Growth Blockers. Cancer Research UK. September 24, 2024.
  3. Ibrance - palbociclib tablet, film coated. Pfizer. September 2025.
  4. Kisqali Highlights of Prescribing Information. Novartis. September 2025.
  5. Verzenio - abemacicle tablet. Eli Lilly and Company. February 2025.
  6. Diéras V et al. Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer. Journal of the National Cancer Institute. April 1, 2019.
  7. De Laurentiis M et al. Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population. Breast Cancer Research and Treatment. October 2021.
  8. Neutropenia. Cleveland Clinic. June 9, 2022.
  9. Best Practices for Managing Patients on CDK4/6 Inhibitors. AJMC. December 13, 2018.
  10. Danahy A. How Nutrition Can Help Fight Cancer Fatigue. American Institute for Cancer Research. October 11, 2023.
  11. Staying on Verzenio: A Guide to Managing Diarrhea. Eli Lilly and Company.
  12. Rugo HS et al. Management of Abemaciclib‐Associated Adverse Events in Patients with Hormone Receptor‐Positive, Human Epidermal Growth Factor Receptor 2‐Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3. The Oncologist. October 9, 2020.
  13. Kisqali. U.S. Food and Drug Administration. October 2022.
  14. Long QT Syndrome (LQTS). Cleveland Clinic. March 20, 2023.
  15. Deep Vein Thrombosis. Cleveland Clinic. March 28, 2022.
  16. Pulmonary Embolism. Cleveland Clinic. February 20, 2024.
  17. Balancing Responsibilities and Self-Care with Metastatic Breast Cancer. Breastcancer.org. August 16, 2023.
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Lisa D. Curcio, MD, FACS

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Lisa Curcio, MD, is a board-certified general surgeon and a fellowship-trained surgical oncologist. She is currently the medical director of breast surgery at Northern Dutchess Hospital in Rhinebeck, New York. Dr. Curcio attended George Washington University Medical School in Washington, D.C., where she also completed a residency in general surgery. She was invited to fellowship training in cancer surgery at City of Hope National Medical Center in Duarte, California. She was the recipient of the competitive U.S. Air Force Health Professions Scholarship Program. During her military commitment, Dr. Curcio served in the military as chief surgical oncologist at Keesler Medical Center in Biloxi, Mississippi. 

From 2003 to 2004, she served as program director for Susan G. Komen in Orange County and remains involved with Komen outreach efforts. She was on the board of Kids Konnected, a nonprofit that helps children of cancer patients deal with the emotional fallout of a cancer diagnosis. Currently, she is on the board at Miles of Hope Breast Cancer Foundation, an organization dedicated to providing support services for people affected by breast cancer in New York's Hudson Valley. Dr. Curcio also has a strong background in breast cancer research, having contributed to dozens of peer-reviewed articles. She is currently a member of the Alpha Investigational Review Board.

Her practice includes benign and malignant breast diagnoses. Dr. Curcio was diagnosed with breast cancer at the age of 37. Although her fellowship training was in surgical oncology, this experience motivated her to provide compassionate, high level breast care and to focus on breast surgery.

Dr. Curcio is passionate about treating the patient and individualizing the care plan to their specific needs. Dr. Curcio strongly believes that cancer care must include lifestyle changes to focus on healthier habits to reduce future events. Her practice also focuses on breast cancer risk reduction, education, and access to genetic testing for patients with a family history of breast cancer.
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Stephanie Watson is a freelance health writer who has contributed to WebMD, AARP.org, BabyCenter, Forbes Health, Fortune Well, Time, Self, Arthritis Today, Greatist, Healthgrades, and HealthCentral. Previously, she was the executive editor of Harvard Women’s Health Watch and Mount Sinai’s Focus on Healthy Aging. She has also written more than 30 young adult books on subjects ranging from celebrity biographies to brain injuries in football.
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