Apalutamide

Prostate Cancer Treatment

Apalutamide is indicated for the treatment of adult patients with two specific forms of prostate cancer:

• Non-metastatic castration-resistant prostate cancer (nmCRPC): This is prostate cancer that has not spread to other parts of the body but continues to progress even when testosterone levels are kept very low through medical or surgical treatment.
• Metastatic castration-sensitive prostate cancer (mCSPC): This is prostate cancer that has spread to other parts of the body and still responds to medical or surgical treatments that lower testosterone levels.

This medication is typically used in combination with androgen deprivation therapy (ADT). This means patients usually continue taking other medications that lower testosterone levels, such as gonadotropin-releasing hormone (GnRH) analogs, or have previously undergone surgical removal of the testicles.

Mechanism of Action

Apalutamide belongs to a class of medications known as androgen receptor inhibitors. It is used to treat prostate cancer by interfering with the hormones that the cancer cells need to survive and multiply.

Prostate cancer cells often depend on male hormones, called androgens (such as testosterone), to grow. Apalutamide works by targeting the androgen receptors within these cells. It functions in three primary ways:

• Blocking hormone binding: The medication attaches to androgen receptors, which prevents testosterone from binding to them.
• Stopping receptor movement: It prevents the androgen receptors from moving into the nucleus of the cancer cell.
• Inhibiting DNA interaction: It stops the receptors from binding with the cell's DNA, a step that is necessary for the cancer cell to grow and divide.

By disrupting these hormonal signals, apalutamide helps slow down the growth of the tumor and can delay the progression of the disease to other parts of the body.

Common Side Effects

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

• Feeling very tired or weak (fatigue)
• Joint, muscle, or bone pain
• Hot flashes
• Diarrhea or nausea
• Decreased appetite and weight loss
• High blood pressure
• Skin rash

Serious Side Effects

Some side effects can be severe and require immediate medical attention. Contact a healthcare provider if you experience:

• Seizures: A loss of consciousness or involuntary shaking.
• Heart problems: Chest pain, shortness of breath, or discomfort in the arms, back, neck, or jaw.
• Stroke symptoms: Sudden numbness or weakness (especially on one side of the body), confusion, or difficulty speaking.
• Severe skin reactions: A widespread rash that may include blistering or peeling skin.
• Falls and fractures: An increased risk of falling which may lead to broken bones.
• Thyroid issues: Symptoms of an underactive thyroid, such as weight gain, constipation, or feeling cold.

Seizure Risk

Apalutamide may increase the risk of seizures. If a seizure occurs during treatment, the medication is typically discontinued permanently. Caution is advised for individuals with a history of seizures or other factors that may increase seizure risk.

Falls and Bone Fractures

There is an increased risk of falls and bone fractures associated with this medication. Healthcare providers may monitor bone health and recommend treatments to help prevent bone loss or fractures during therapy.

Heart Disease and Stroke

Serious heart-related problems, including heart attacks and chest pain (ischemic heart disease), have occurred in patients taking apalutamide. Some cases have been fatal. There is also a risk of ischemic stroke. Monitoring for signs and symptoms of cardiovascular issues is common practice.

Severe Skin Reactions

Severe and potentially life-threatening skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been reported. Treatment should be stopped if a severe skin reaction is suspected.

Thyroid Function

Apalutamide can cause hypothyroidism (underactive thyroid). Healthcare providers may perform blood tests to monitor thyroid-stimulating hormone (TSH) levels before and during treatment.

Reproductive Risks

Apalutamide can cause harm to a developing fetus and is not intended for use in women. Men with female partners who could become pregnant should use effective contraception during treatment and for three months after the final dose. Men should also use a condom when having sex with a pregnant woman.

Pregnancy and Contraception

Apalutamide is not indicated for use in women. This medication can cause significant harm to a developing fetus or lead to pregnancy loss if a pregnant woman is exposed. Because the drug can be present in semen, men taking apalutamide must follow specific safety precautions:

• Men with female partners who are able to become pregnant should use effective birth control during treatment and for 3 months after the final dose.
• Men should use a condom during sexual activity with a pregnant woman to prevent the medication from reaching the fetus.

Breastfeeding

It is not known if apalutamide passes into human breast milk or what effects it might have on a nursing infant. The medication is not intended for use in females, and there is no clinical data regarding its safety during breastfeeding.

Fertility

Apalutamide may impair male fertility. Based on its mechanism of action and animal studies, the medication may decrease the ability to father a child. It is not known if these effects on fertility are reversible.

Dosage Forms

Apalutamide is supplied as a film-coated tablet intended for oral administration. It is designed to be swallowed whole, though healthcare providers may provide specific instructions for patients who have difficulty swallowing tablets.

• Oral tablet

FDA Approval History

Apalutamide received its initial approval from the U.S. Food and Drug Administration (FDA) in February 2018. It was the first treatment approved for patients with non-metastatic castration-resistant prostate cancer (nmCRPC). In September 2019, the FDA expanded its approval to include the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).

Approved Indications

Apalutamide is currently indicated for the treatment of:

• Metastatic castration-sensitive prostate cancer (mCSPC): Prostate cancer that has spread to other parts of the body and still responds to medical or surgical treatment that lowers testosterone.
• Non-metastatic castration-resistant prostate cancer (nmCRPC): Prostate cancer that has not spread to other parts of the body but no longer responds to medical or surgical treatment that lowers testosterone.

Safety and Monitoring

The FDA monitors the safety of apalutamide through the FDA Adverse Event Reporting System (FAERS). In 2020, the FDA identified potential signals of serious risks, including ischemic heart disease and cerebrovascular accidents, based on post-marketing reports. The drug does not currently have a Boxed Warning or a Risk Evaluation and Mitigation Strategy (REMS) program.

Brand and Generic Status

Apalutamide is only available as a brand-name drug. There is currently no generic version on the market. Generic drugs usually cost less than brand-name drugs, so the lack of a generic option may contribute to higher treatment costs.

Factors Affecting Cost

The actual price a patient pays for apalutamide can vary based on several factors:

• Insurance Coverage: Most insurance plans and Medicare Part D cover apalutamide, but it is typically classified as a specialty drug, which may require a higher copayment or coinsurance.
• Pharmacy Type: This medication is often dispensed through specialty pharmacies rather than standard retail pharmacies, which can influence the final price.
• Treatment Duration: The total cost is determined by how long the healthcare provider prescribes the medication.

Financial Assistance Options

Financial assistance may be available to help manage the cost of apalutamide. The manufacturer often provides savings programs or copay cards for patients with commercial insurance. Additionally, patient assistance programs may help those who are uninsured or underinsured and meet certain eligibility requirements.