Truqap

Approved Uses

Truqap is indicated for the treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. It is used when the cancer is locally advanced and cannot be removed by surgery, or when it has spread to other parts of the body (metastatic).

Genetic Testing Requirements

This medication is specifically for patients whose tumors have one or more abnormal genetic alterations. These include:

• PIK3CA
• AKT1
• PTEN

A healthcare provider will use an FDA-approved test to confirm the presence of these specific gene changes before starting treatment with Truqap.

Treatment Context

Truqap is used in combination with another cancer medicine called fulvestrant. It is generally prescribed for patients whose cancer has returned or worsened during or after receiving hormone therapy. This includes situations where the cancer progressed while the patient was taking endocrine-based regimens for metastatic disease or within a certain timeframe after completing treatment for early-stage cancer.

Targeting the AKT Pathway

Truqap belongs to a class of medications known as kinase inhibitors. Its active ingredient, capivasertib, specifically targets a protein in the body called AKT (also known as protein kinase B). This protein plays a critical role in a signaling pathway that regulates how cells grow, divide, and survive.

How It Affects Cancer Cells

In some types of breast cancer, the AKT pathway becomes overactive due to genetic mutations or alterations in genes such as PIK3CA, AKT1, or PTEN. When this pathway is stuck in the "on" position, it sends continuous signals for cancer cells to multiply uncontrollably and resist natural cell death.

Truqap works by:

• Binding to AKT: The medication attaches to and blocks three versions of the AKT protein (AKT1, AKT2, and AKT3).
• Interrupting Signals: By inhibiting these proteins, Truqap disrupts the signaling pathway that fuels cancer growth.
• Slowing Progression: This interference helps slow down the growth of the tumor and may cause cancer cells to die.

Because Truqap targets a specific molecular process, it is often used for patients whose tumors have been tested and shown to have specific genetic changes that make the cancer dependent on the AKT pathway.

Common Side Effects

Many people taking Truqap experience mild to moderate side effects. These may include:

• Diarrhea
• Nausea and vomiting
• Fatigue or weakness
• Mouth sores or inflammation (stomatitis)
• Headache
• Rash
• Decreased appetite

Serious Side Effects

Some side effects can be severe and require immediate medical attention. Contact your doctor right away if you experience:

• Severe diarrhea: This can lead to significant fluid loss and dehydration.
• High blood sugar (hyperglycemia): Symptoms may include excessive thirst, frequent urination, blurred vision, or fruity-smelling breath.
• Severe skin reactions: Watch for rashes that cover a large area, or skin that blisters, peels, or becomes painful.
• Low blood cell counts: This may manifest as unusual bruising, pale skin, or signs of infection like fever and chills.
• Kidney problems: Indicated by changes in laboratory tests or decreased urination.

Hyperglycemia

Truqap can cause significant increases in blood sugar levels, even in patients who do not have a history of diabetes. Healthcare providers typically monitor fasting blood glucose and hemoglobin A1c levels before starting treatment and at regular intervals during therapy. If blood sugar becomes too high, the medication dose may be reduced, paused, or permanently stopped.

Severe Diarrhea

Diarrhea is a common side effect that can become severe and lead to dehydration. Healthcare providers may recommend starting anti-diarrheal medication at the first sign of loose stools and increasing fluid intake. If diarrhea is severe or persistent, the Truqap dosage may need to be adjusted.

Skin Reactions

Serious and potentially life-threatening skin reactions, including rashes that blister or peel, have occurred in patients taking this medication. It is important to report any new or worsening skin changes to a healthcare provider immediately, as severe reactions may require stopping the treatment.

Embryo-Fetal Toxicity

Based on its mechanism of action, Truqap can cause harm to a developing fetus. Healthcare providers typically perform a pregnancy test for individuals of reproductive potential before starting treatment. The following precautions are generally recommended:

• Females who can become pregnant should use effective birth control during treatment and for at least one month after the final dose.
• Males with female partners of reproductive potential should use effective contraception during treatment and for at least four months after the final dose.

Pregnancy

Truqap may cause harm to a developing fetus if taken during pregnancy. Healthcare providers typically require a pregnancy test before starting treatment to ensure the patient is not pregnant. If you are pregnant or planning to become pregnant, it is important to discuss the potential risks to the fetus with your medical team.

Contraception Requirements

Because of the potential for fetal harm, specific birth control measures are recommended for both women and men during and after treatment:

• Females: Women who are able to become pregnant should use effective birth control during treatment and for at least 1 month after the final dose.
• Males: Men with female partners who are able to become pregnant should use effective birth control during treatment and for at least 4 months after the final dose.

Breastfeeding

It is not known whether Truqap passes into breast milk. Because of the potential for serious side effects in a nursing infant, breastfeeding is not recommended during treatment and for at least 1 month after the last dose of the medication.

Available Forms

Truqap is available as a film-coated tablet for oral administration.

FDA Approval Status

The U.S. Food and Drug Administration (FDA) approved Truqap (capivasertib) in November 2023. It is approved for use in combination with fulvestrant for adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer.

Approved Indications

Truqap is specifically indicated for patients whose tumors have one or more genetic alterations in the following genes:

• PIK3CA
• AKT1
• PTEN

The medication is used when the cancer has progressed after at least one endocrine-based treatment in the metastatic setting, or has returned within 12 months of completing adjuvant therapy.

Diagnostic Requirements

Because Truqap is only for patients with specific genetic markers, the FDA also approved a companion diagnostic test to identify eligible patients. Healthcare providers must confirm the presence of PIK3CA, AKT1, or PTEN alterations using an FDA-approved test before starting treatment.

Safety and Monitoring

There are currently no Boxed Warnings or Risk Evaluation and Mitigation Strategies (REMS) required for Truqap. The approval was based on clinical trial data showing improved progression-free survival compared to treatment with fulvestrant alone.

There is currently no evidence that Truqap (capivasertib) causes physical dependence or a withdrawal syndrome when the medication is discontinued. Unlike medications that affect the central nervous system, stopping this targeted therapy does not typically result in physical symptoms like those seen with the cessation of opioids or certain antidepressants.

However, it is important to consider the following regarding the discontinuation of treatment:

• Disease Progression: Truqap is used to treat specific types of advanced breast cancer. Stopping the medication may allow the cancer to grow or spread more quickly, as the drug will no longer be present to inhibit the proteins that help cancer cells survive.
• Dosing Schedule: Truqap is typically taken on a specific cycle, such as four days of treatment followed by three days off. It is important to follow this schedule exactly as prescribed to maintain the drug's effectiveness.
• Medical Supervision: You should not stop taking Truqap or change your dose unless your doctor instructs you to do so. If you are experiencing severe side effects, such as high blood sugar, severe diarrhea, or skin rashes, your doctor may recommend pausing the medication or reducing the dose rather than stopping it permanently.