What Are the Clinical Uses of Capivasertib?
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Capivasertib: Redefining the Fight Against Breast Cancer

Published on Feb 12, 2024 and last reviewed on Feb 20, 2024   -  11 min read

Abstract

Capivasertib is a medication used in treating advanced breast cancer by inhibiting abnormal protein signals.

Overview

For the treatment of breast cancer, a drug called Capivasertib is used. It is used explicitly for Human epidermal growth factor receptor 2 (HER2)-negative, hormone receptor-positive breast cancer that has spread locally or metastasized. It is common practice to combine Capivasertib with Fulvestrant, another drug for breast cancer. The United States Food and Drug Administration (USFDA) approved Capivasertib on 16 November, 2023.

Drug Group:

Capivasertib belongs to the class of drugs known as kinase inhibitors, which specifically target enzymes involved in cell division and proliferation. Capivasertib acts as a treatment for advanced breast cancer by blocking abnormal proteins that are essential in triggering the growth of cancer cells. Capivasertib can slow down or prevent the spread of cancer cells by interfering with this signaling system. Because of this mechanism, Capivasertib is a valuable tool in the all-encompassing management of advanced breast cancer, significantly when the cancer has progressed to other body parts. The medication functions as a precision medicine in treating this particular type of cancer because of its targeted action on particular cellular processes.

Indications:

Capivasertib is authorized for the treatment of individuals with a certain kind of metastatic or advanced breast cancer when combined with Fulvestrant. Human epidermal growth factor receptor 2 (HER2), hormone receptor (HR) positivity, and certain genetic modifications known as PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) or AKT1 (AKT Serine or Threonine Kinase 1) or PTEN (Phosphatase and Tensin Homolog) abnormalities are required for this cancer. An FDA-approved test is required to verify these changes. Patients whose cancer has returned within a year of finishing adjuvant therapy or whose cancer has progressed after trying at least one hormonal therapy in the advanced stage are advised to pursue this treatment.

Contraindications:

Capivasertib should not be used in patients with a strong allergic reaction (severe hypersensitivity) to Capivasertib.

Dosage Forms and Available Strengths

Tablets are medications that come in two strengths:

  • 160 mg (Milligram) Tablets: These are round, beige, and have a film coating. They have 'CAV' above '160' engraved on one side, and the other is plain.

  • 200 mg Tablets: These are capsule-shaped, beige, and have a film coating. On one side, they are marked with 'CAV 200,' and the other side is plain.

For Patients

What Is Breast Cancer?

Uncontrollably proliferating breast cells result in breast cancer. Breast cancer comes in different forms, and the kind that affects a person relies on which breast cells develop cancerous cells. Breast cancers frequently originate in the ducts or lobules of the breast. When breast cancer spreads to other areas of the body through lymphatic and blood vessels, it is referred to as metastasis.

What Are the Clinical Uses of Capivasertib?

How Should Capivasertib Be Used?

Capivasertib is given orally as pills twice a day, about 12 hours apart, with or without food, for the first four days of a seven-day cycle. The doctor will determine how often to repeat the cycle. It is recommended that the tablets be consumed whole, with water, without being divided, chewed, or crushed. Capivasertib should not be taken if vomiting occurs; the usual dosing regimen should be continued the next day. The doctor may change the dosage or course of treatment for Capivasertib depending on how the individual responds to it and any side effects they experience. Even if one feels better, it is crucial to keep taking Capivasertib; in fact, one should only stop taking it after talking to their doctor. When treating breast cancer, patients who have not gone through menopause or who are in the early stages may also be prescribed Goserelin or Leuprolide in addition to Capivasertib and Fulvestrant.

What Is the Prescribed Dosage and Method of Administration for Capivasertib?

  • Choosing a Patient: Patients with advanced or metastatic breast cancer that are HR-positive, HER2-negative, and have specific genetic alterations (PIK3CA, AKT1, PTEN) should be selected for Capivasertib treatment.

  • Assessment Suggested Before Beginning Capivasertib: One should check glycated hemoglobin (HbA1C) and fasting blood glucose (FG) levels before beginning Capivasertib. This evaluation aims to identify potential problems, and it should be performed both before and often during treatment.

  • Suggested Dosage and Administration: 400 mg twice daily for four days, followed by three days off, is the recommended Capivasertib dose when taken with Fulvestrant. This cycle continues until the disease worsens or its adverse effects become intolerable. Capivasertib tablets should be swallowed whole; do not break or crush them.

  • Adjustments to Dosage for Severe and Mild CYP3A Inhibitors: Strong CYP3A (Cytochrome P450 3A) inhibitors should not be taken with Capivasertib. The doctor will lower the dosage of Capivasertib if it cannot be avoided. Modest CYP3A inhibitors should have the dosage changed appropriately. Once these inhibitors are stopped, after three to five half-lives of the inhibitor, return to the Capivasertib dosage given before starting the inhibitor.

What Are the Side Effects of Capivasertib?

There may be adverse effects from Capivasertib. Contact the doctor if a person experiences any of the following symptoms, especially if they are severe or continue:

  • Throwing up.

  • Reduced appetite.

  • Weakness.

  • Headache.

  • Dysentery (an intestinal infection that results in bloody diarrhea).

  • Oral lesions.

Some adverse effects may be dangerous. The following symptoms should be noticed immediately. Stop taking the drug, call the doctor, or get emergency care.

  • Fever and symptoms similar to flu.

  • Frequent, loose, or watery feces; cramping in the stomach.

  • Weakness, reduced urine, dry mouth, and ankle or leg swelling.

  • Rash, blistering (lips, eyes, or mouth), peeling, dry, or reddish skin.

Furthermore, Capivasertib may have other adverse effects. If a person experiences any odd issues while taking this drug, they should get in touch with their doctor.

What Are the Things to Inform the Doctor Before Taking Capivasertib?

  • Allergies: Let the physician and pharmacist know if the person has any allergies to Capivasertib, other drugs, or the chemicals in the tablet form. Ask the pharmacist for an ingredient list.

  • Drug Interaction: Inform the doctor about the prescription and over-the-counter drug regimens, vitamins, supplements, and herbal remedies the person consumes. Dosage modifications or adverse effect monitoring might be required. It is advisable to consult with the doctor about using St. John's Wort before beginning Capivasertib.

  • Medical Conditions: Inform the doctor of skin conditions, elevated triglyceride (cholesterol) levels, and kidney or liver difficulties.

  • Pregnancy: See a doctor if the individual is pregnant, intends to become pregnant, or is thinking about becoming a father. Pregnancy testing could be necessary before starting therapy. One should use reliable birth control both during and after therapy to minimize the risk to the developing fetus.

  • Breastfeeding: The patient should avoid nursing while using Capivasertib.

  • Monitoring Blood Glucose: Remember that Capivasertib may cause blood glucose levels to rise. The patient should check blood sugar levels if they have diabetes, as instructed by the physician. If one has symptoms such as intense thirst, frequent urination, hunger, dizziness, disorientation, or weakness, they should get in touch with their doctor. Reporting nausea, vomiting, or diarrhea as soon as possible is essential since blood sugar control may need dietary or prescription modifications.

Dietary Consideration: One should avoid eating grapefruit or drinking grapefruit juice while using this medication.

Storage: Make sure the container is securely closed, and keep the medication in the same container it arrived in. The medicine should be stored at room temperature, away from sources of heat or moisture, and not in the restroom. It is essential to keep the medication out of children's reach because they can readily open containers like weekly pill organizers. Keep all medications out of children's reach and sight to avoid accidental consumption.

Disposal: Once the drug Capivasertib has served its purpose, dispose of it in a manner that poses no risk to children, pets, or others. Capivasertib should not be flushed down the toilet. The best course of action is to implement a medication take-back program. To learn more about take-back initiatives in the neighborhood, speak with the pharmacist or contact the recycling or trash department.

Missed Dose: One should take the missed dose as soon as remembered. On the other hand, skip the missed dose and carry on with the regular dosing plan if over four hours have elapsed since the scheduled time. Avoid taking two doses to make up for the one that is missed.

Overdose: If someone takes too much of this medicine, call the poison control helpline. If the person collapses, has a seizure, struggles to breathe, or cannot be woken up, dial emergency services right away.

For Doctors

Pharmacodynamics:

  • Relationships Between Exposure and Response: The exact relationship between the body's level of Capivasertib and its effectiveness and the duration of time it takes to show results is unknown. However, researchers did notice that at doses between 80 and 800 mg, or 0.2 to two times the average recommended dosage, some adverse effects such as diarrhea, dermatitis, and elevated blood sugar levels were more likely to occur.

  • Electrophysiology of the Heart: The QTc interval, which measures how long it takes the heart to recharge between beats, did not significantly increase at the normal dose of Capivasertib in terms of the heart's electrical activity.

Mechanism of Action: Capivasertib is a medication that inhibits the function of the AKT protein, which is involved in the development of cancer cells. Capivasertib inhibits all three types of AKT (AKT1, AKT2, and AKT3). Activation of AKT in cancers is typically caused by mutations in AKT itself, modifications to associated proteins such as PIK3CA, or loss of a protein known as PTEN.

Capivasertib showed the ability to inhibit the growth of breast cancer cells in vitro, particularly those with specific mutations in AKT1, PIK3CA, or PTEN. In in vivo experiments on animals, Capivasertib, either by itself or in combination with Fulvestrant, effectively inhibited the growth of tumors in mice. This comprises models of breast cancer with alterations in AKT1, PTEN, and PIK3CA.

Pharmacokinetics: Unless otherwise noted, the mean [%coefficient of variation (% CV)] represents the Capivasertib pharmacokinetic characteristics. The Cmax (the highest concentration of a drug in the blood) is 1,371 ng/mL - nanograms per milliliter (30 percent), and the steady-state AUC is 8,069 h·ng/mL (37 percent). Beginning in week two, concentrations normalize on the third and fourth dosage days of every week. On days without dosage, plasma concentrations range from 0.5 percent to 15 percent of the steady-state Cmax. Within the range of 80 to 800 mg (0.2 to 2 times the recommended dosage), AUC and Cmax are dose-related.

  • Absorption: Tmax (peak time of drug concentration) is roughly one to two hours, and 29 percent of the drug has absolute bioavailability.

  • Impact of Food: Following treatment with either a low-fat meal (about 400 kcal; fat 26 percent) or a high-fat meal (roughly 1,000 kcal; fat 60 percent), no clinically significant variations in Capivasertib pharmacokinetics were detected.

  • Distribution: The oral volume of distribution in a steady state is 1,847 L-liter (36 percent). The ratio of plasma to blood is 0.71, and the plasma protein binding is 22 percent.

  • Elimination: Renal clearance makes up 21 percent of total clearance, the half-life is 8.3 hours, and steady-state oral clearance is 50 L/h - liters per hour (37 percent CV).

  • Metabolism: CYP3A4 and UGT2B7 (UDP Glucuronosyltransferase 2 Family, Polypeptide B7) are mainly responsible for the metabolism of Capivasertib.

  • Excretion: The mean total recovery after a single 400 mg radiolabeled oral dosage was 50 percent from feces and 45 percent from urine.

Drug Interactions:

  • Strong Inhibitors of CYP3A: Capivasertib may be exposed to higher levels when taken with potent CYP3A inhibitors. This increased exposure increases the chance that Capivasertib will have adverse side effects. To mitigate this, it is strongly advised to avoid using Capivasertib in combination with potent CYP3A inhibitors. If avoidance is not an option, it is advised to lower the amount of Capivasertib while closely monitoring patients for any possible adverse effects.

  • Moderate Inhibitors of CYP3A: When used with Capivasertib, moderate CYP3A inhibitors have the same potential to increase exposure to Capivasertib as potent inhibitors. Capivasertib is more likely to cause adverse reactions as a result of this higher exposure. To manage this, it is recommended to lower the dose of Capivasertib when co-administered with a moderate CYP3A inhibitor. Patients using this combination should be continuously observed for any possible adverse effects.

  • Potent and Mild CYP3A Inducers: Conversely, exposure to Capivasertib is reduced by strong or moderate CYP3A inducers. This decrease in exposure may jeopardize the effectiveness of Capivasertib. To alleviate this worry, it is advised against taking Capivasertib in conjunction with strong or moderate CYP3A inducers. Preserving Capivasertib's therapeutic efficacy in treating the intended illnesses is the goal.

Clinical Studies: The efficacy of Capivasertib in combination with Fulvestrant was investigated in a trial comprising 708 adult patients with HER2-negative, HR-positive, locally progressed, or metastatic breast cancer. Progression-free survival (PFS) was significantly improved by the trial both in the general population and in patients with PIK3CA or AKT1 or PTEN abnormalities in particular. Major outcomes included PFS, overall survival, objective response rate, and durability of response. Patients received either Capivasertib or a placebo. Patients with PIK3CA, AKT1, or PTEN changes benefited significantly from the trial, indicating that Capivasertib is helpful in this particular group. The research provided important insights into the effectiveness of Capivasertib by considering several variables, including age, race, and prior treatments.

Warnings and Precautions:

  • Hyperglycemia: The medicine Capivasertib may cause hyperglycemia or elevated blood sugar. Some patients experienced severe instances, particularly those who required insulin or had type 1 diabetes. Hyperglycemia occurred in approximately 18 percent of patients, with severe cases occurring in 2.8 percent of cases. It is essential to regularly check blood sugar levels, and patients should call their doctor if they experience symptoms like increased thirst or urination. It may be necessary to modify the course of treatment, and a lifestyle change is advised.

  • Diarrhea: Capivasertib can induce diarrhea, and in severe cases, dehydration may result. Diarrhea struck 72 percent of patients, with nine percent suffering from severe cases. It is crucial to watch for symptoms; people who experience diarrhea should start taking antidiarrheal medication as soon as it appears. Depending on the severity, dose modifications or cessation can be required.

  • Cutaneous Adverse Reactions: When using Capivasertib, patients may have skin reactions such as palmar-plantar erythrodysesthesia (redness and pain on palms and soles due to chemotherapy) or erythema multiforme (target-like lesions caused by drugs or illnesses). Of the patients, 58 percent had these, with 17 percent having severe instances. It is essential to keep an eye out for skin responses, and seeing a dermatologist as soon as possible is advised. Depending on the severity, changes to the treatment may be necessary.

  • Embryo-Fetal Toxicity: Research on animals has shown that Capivasertib can be harmful to a developing fetus. Effective contraception should be used both during and after therapy for persons who are pregnant or who may become pregnant in the future. Male patients should utilize contraception if they have female partners who are capable of having children. The drug is used in conjunction with Fulvestrant; further details on pregnancy and contraception are included in the prescribing information for Fulvestrant.

Use in Specific Populations:

  • Pregnancy: If Capivasertib is used with Fulvestrant, the growing fetus may suffer. Women who are pregnant or intend to become pregnant should review the complete Fulvestrant information. Pregnant women or those who may become pregnant should be informed of the hazards, as animal studies have demonstrated negative consequences. Since there is no information about Capivasertib use during human pregnancy, caution is advised.

  • Lactation: It is unclear how Capivasertib will affect nursing. There is a lack of information regarding Capivasertib in human milk, and it is advisable to use caution as it may cause harm to a breastfeeding infant.

  • Reproductive Potential: Pregnancy testing is advised before beginning treatment since Capivasertib can be harmful to a fetus. It is recommended that women use effective contraception during and for one month following treatment and that men who have female partners use contraception for four months following the final dose.

  • Pediatric Use: There is no proof of the safety or efficacy of Capivasertib in kids.

  • Geriatric Use: Compared to younger patients, patients over 65 had increased rates of severe adverse events, dose modifications, interruptions, and permanent discontinuations, but there were no appreciable variations in Capivasertib's effectiveness.

  • Renal Impairment: Mild to severe renal impairment does not require dose modification. There are no data on severe renal impairment.

  • Hepatic Impairment: It is not advisable to change the dosage in cases of minor hepatic impairment. Caution is suggested as moderate impairment may enhance exposure to Capivasertib. There are no data available on severe liver impairment.

Last reviewed at:
20 Feb 2024  -  11 min read

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