Kisqali

Advanced or Metastatic Breast Cancer

Kisqali is used to treat hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer that is advanced or has spread to other parts of the body (metastatic). It is prescribed in the following situations:

• In combination with an aromatase inhibitor as the first hormone-based therapy for postmenopausal women.
• In combination with fulvestrant as the first hormone-based therapy or after the cancer has progressed during other hormone treatments.
• For men and premenopausal or perimenopausal women when used with appropriate hormone suppression therapy.

  Early Breast Cancer

  Kisqali is also approved for use in adults with HR+, HER2- early breast cancer (Stage II or III) that is at a high risk of returning. In these cases, it is used as an adjuvant treatment, which is therapy given after the primary treatment (such as surgery). It is used in combination with an aromatase inhibitor to help lower the risk of the cancer coming back.

Mechanism of Action

Kisqali belongs to a class of drugs known as kinase inhibitors. Specifically, it is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. These proteins are found in both normal and cancer cells, but they play a critical role in controlling how fast cells grow and divide.

How CDK4/6 Inhibitors Work

In certain types of breast cancer, the CDK4 and CDK6 proteins become overactive, which causes cancer cells to multiply rapidly. Kisqali works by:

• Blocking protein signals: It attaches to the CDK4 and CDK6 proteins to prevent them from signaling the cell to divide.
• Slowing cancer progression: By interfering with these signals, the medication helps slow the growth of the tumor and may stop the cancer cells from dividing altogether.

Combination with Hormone Therapy

Kisqali is typically used in combination with hormone therapies, such as aromatase inhibitors or fulvestrant. While hormone therapy works by reducing or blocking estrogen that fuels the cancer, Kisqali works at a different stage by directly targeting the cell division cycle. Using these treatments together provides a dual approach to stopping cancer cell growth.

Common Side Effects

• Nausea and vomiting
• Diarrhea or constipation
• Fatigue and weakness
• Hair thinning or hair loss
• Headache
• Back pain
• Rash
• Mouth sores
• Cough

Serious Side Effects

Some side effects can be severe and require immediate medical attention. Seek help if you experience:

• Infections: Fever, chills, or other signs of infection, which may indicate low white blood cell counts.
• Liver Problems: Yellowing of the skin or eyes, dark urine, pain in the upper right stomach area, or loss of appetite.
• Heart Rhythm Changes: Dizziness, fainting, or a fast, irregular, or pounding heartbeat.
• Lung Inflammation: New or worsening shortness of breath, cough, or chest pain.
• Severe Skin Reactions: Skin pain, reddening, or blistering and peeling of the skin.

Heart Rhythm Changes

Kisqali can cause a condition called QT interval prolongation, which affects the heart's electrical rhythm. This can lead to serious heart rhythm disturbances. Healthcare providers typically perform electrocardiograms (ECGs) and blood tests to check electrolyte levels, such as potassium and magnesium, before starting and during treatment.

Liver Toxicity

This medication may cause severe liver inflammation or damage. Liver function tests are usually conducted before starting therapy and at regular intervals during the first few months of treatment. Signs of liver issues include yellowing of the skin or eyes (jaundice), dark urine, or pain in the upper right stomach area.

Lung Inflammation

Severe or life-threatening lung inflammation, known as interstitial lung disease or pneumonitis, has been reported with the use of Kisqali. Monitoring for new or worsening respiratory symptoms such as cough, chest pain, or shortness of breath is standard practice during treatment.

Low White Blood Cell Counts

Neutropenia, a decrease in white blood cells that fight infection, is a common side effect. Frequent blood counts are necessary to monitor these levels. Fever or other signs of infection should be reported to a healthcare provider immediately.

Severe Skin Reactions

Rare but serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, can occur. Symptoms may include peeling skin, blisters, or sores on the mucous membranes, such as the lips or mouth.

Pregnancy and Fetal Risk

Kisqali can cause harm to a developing fetus. Effective birth control is recommended for individuals of reproductive potential during treatment and for at least three weeks after the final dose. Breastfeeding is not recommended during treatment and for three weeks after the last dose.

Pregnancy Considerations

Kisqali can cause fetal harm if taken during pregnancy. Based on findings from animal studies, the medication may lead to birth defects or pregnancy loss. Healthcare providers typically require a pregnancy test to ensure a patient is not pregnant before starting treatment.

Individuals who can become pregnant should use effective birth control during treatment and for at least 3 weeks after the final dose. If a patient becomes pregnant while taking this medication, they should contact their healthcare provider immediately to discuss the potential risks.

Breastfeeding

It is not known whether Kisqali passes into human breast milk. Because of the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment and for at least 3 weeks after the last dose.

Fertility

Based on animal studies, Kisqali may impair fertility in males. Patients should discuss any concerns regarding reproductive health and future family planning with their healthcare team before starting treatment.

Available Forms

Kisqali is provided as film-coated tablets for oral administration. The tablets are typically packaged in blister cards to help track the treatment cycle.

The medication is available in the following formats:

• Kisqali: A package containing only ribociclib tablets.
• Kisqali Femara Co-Pack: A combination package that contains both Kisqali tablets and letrozole tablets for use together.

FDA Approval Status

Kisqali (ribociclib) was first approved by the U.S. Food and Drug Administration (FDA) in March 2017. It belongs to a class of drugs known as kinase inhibitors. Since its initial release, the FDA has expanded its approved uses to include various stages of breast cancer treatment.

Approved Uses

Kisqali is FDA-approved for adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in the following scenarios:

• Advanced or Metastatic Cancer: It is used in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy or after the cancer has progressed on other hormonal treatments.
• Early-Stage Cancer: In 2024, the FDA approved Kisqali for use with an aromatase inhibitor to treat patients with early-stage breast cancer who have a high risk of the cancer coming back (recurrence).

Regulatory Warnings and Safety Communications

The FDA has issued safety alerts for the class of drugs Kisqali belongs to (CDK4/6 inhibitors). This includes a warning about the potential for rare but serious lung inflammation, such as interstitial lung disease or pneumonitis. Healthcare providers are advised to monitor patients for new or worsening respiratory symptoms.

There are currently no Boxed Warnings or Risk Evaluation and Mitigation Strategy (REMS) programs required for Kisqali. However, the FDA continues to monitor its safety through post-marketing surveillance, particularly regarding its effects on heart rhythm (QT prolongation) and liver function.

Insurance and Out-of-Pocket Costs

Kisqali is a specialty medication, and its price can vary significantly based on the patient's insurance plan. Most commercial insurance and Medicare Part D plans provide coverage, but patients may still be responsible for co-pays, deductibles, or co-insurance. Because it is a specialty drug, it is often dispensed through specific specialty pharmacies rather than standard retail locations.

Financial Assistance Programs

There are several resources available to help manage the cost of Kisqali treatment:

• Co-pay Savings Cards: Patients with commercial (private) insurance may be eligible for manufacturer programs that reduce out-of-pocket costs to a minimal amount per prescription.
• Patient Assistance Programs: For individuals without insurance or those who are underinsured, the manufacturer may provide the medication at no cost or a reduced rate based on financial need.
• Independent Foundations: Some non-profit organizations offer financial grants to help cancer patients cover the costs of their medications and insurance premiums.

Patients should consult with their healthcare team or a financial counselor at their treatment center to explore these options and determine the most accurate cost for their specific situation.