Trodelvy

Breast Cancer

Trodelvy is approved to treat two specific types of breast cancer that are locally advanced or metastatic, meaning the cancer has spread to other parts of the body or cannot be removed by surgery:

• Triple-negative breast cancer (TNBC): It is used for adults who have already received at least two prior treatments for their cancer, including at least one treatment for metastatic disease.
• HR-positive, HER2-negative breast cancer: It is used for adults who have already received hormonal (endocrine) therapy and at least two other systemic treatments for metastatic disease.

Urothelial Cancer

Trodelvy is also used to treat adults with advanced or metastatic urothelial cancer, which is a type of cancer that affects the bladder and urinary tract. It is typically prescribed after the patient has already been treated with:

• A platinum-containing chemotherapy.
• An immunotherapy medicine.

For urothelial cancer, this medication received accelerated approval based on early study results. Continued approval may depend on the results of ongoing clinical trials to confirm its clinical benefit.

Targeted Delivery

Trodelvy is an antibody-drug conjugate, which means it combines a monoclonal antibody with a chemotherapy medication. The antibody portion is designed to recognize and attach to a protein called Trop-2, which is found on the surface of many types of cancer cells.

Mechanism of Action

The process of how Trodelvy works involves several steps:

• Binding: The antibody travels through the body and attaches to the Trop-2 protein on the cancer cell surface.
• Internalization: Once attached, the cancer cell absorbs the entire Trodelvy molecule.
• Release: Inside the cell, the chemotherapy drug (SN-38) is released from the antibody.
• Cell Death: The chemotherapy drug prevents the cancer cell from repairing its DNA. This damage stops the cell from dividing and eventually causes it to die.

By targeting cells that express Trop-2, Trodelvy aims to deliver a potent dose of chemotherapy directly to the tumor while minimizing exposure to healthy cells that lack this protein.

Common Side Effects

Many people receiving Trodelvy experience side effects during treatment. Common symptoms include:

• Nausea and vomiting
• Diarrhea or constipation
• Feeling very tired or weak (fatigue)
• Hair loss (alopecia)
• Decreased appetite
• Rash
• Stomach-area (abdominal) pain
• Cough or shortness of breath

Serious Side Effects

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

• Severe diarrhea: This can lead to dangerous dehydration. Seek help for frequent or loose stools that do not stop or if you cannot drink enough fluids.
• Low white blood cell count (neutropenia): This is a serious condition that increases your risk of life-threatening infections. Watch for fever, chills, sore throat, or other signs of illness.
• Infusion-related reactions: Some patients react during or shortly after the injection. Symptoms may include skin rash, hives, fever, wheezing, or dizziness.
• Severe nausea and vomiting: If you are unable to keep fluids down or if prescribed anti-nausea medications are not effective.
• Kidney problems: Signs may include changes in urine color or amount, or swelling in the legs and feet.

Boxed Warnings

Trodelvy carries boxed warnings for two serious conditions that may be life-threatening:

• Severe Neutropenia: This medication can cause a dangerous drop in white blood cell counts, increasing the risk of severe or fatal infections. Blood counts are monitored before each dose, and treatment may be delayed or the dose reduced if counts are too low.
• Severe Diarrhea: Severe diarrhea can occur, potentially leading to dehydration and electrolyte imbalances. Healthcare providers monitor for this symptom and may prescribe medications like loperamide to be used at the first sign of loose stools.

Infusion-Related Reactions

Serious hypersensitivity reactions, including anaphylaxis, have occurred during or shortly after administration. Patients are typically monitored for at least 30 minutes following each infusion. Premedication with antihistamines or other drugs is standard practice to reduce this risk.

Nausea and Vomiting

Trodelvy is associated with a high risk of nausea and vomiting. Preventive anti-nausea medications are usually administered before each dose to help manage these side effects.

Genetic Risk Factors

Patients with a specific genetic variation known as the UGT1A1*28 allele are at an increased risk for severe neutropenia and other side effects. Healthcare providers may consider this factor when determining the safety of the treatment.

Embryo-Fetal Toxicity

This medication can cause fetal harm if administered to a pregnant woman. Females of reproductive potential are advised to use effective contraception during treatment and for six months after the last dose. Males with female partners of reproductive potential should use effective contraception during treatment and for three months after the last dose.

Pregnancy Risks

Trodelvy can cause harm to a fetus if taken during pregnancy. Healthcare providers typically require a pregnancy test for individuals of reproductive potential before starting this medication. If you are pregnant or planning to become pregnant, it is important to discuss the risks with your medical team.

Contraception

Because of the risks to a developing fetus, specific precautions regarding birth control are recommended:

• For females: Use effective contraception during treatment and for 6 months after the last dose.
• For males: Use effective contraception during treatment and for 3 months after the last dose if your partner can become pregnant.

Breastfeeding Considerations

It is currently unknown if Trodelvy passes into breast milk. Due to the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment and for at least 1 month following the final dose. Consult with a healthcare provider to discuss safe infant feeding options during this period.

Dosage Forms

Trodelvy is supplied as a sterile, preservative-free, lyophilized powder in a single-dose vial. It is intended for reconstitution and further dilution by a healthcare professional before use.

Administration Method

This medication is administered only as an intravenous infusion. It is not given as an intravenous push or bolus, and it is not available in oral forms such as tablets or capsules.

FDA Approval Status

Trodelvy received its initial FDA approval in April 2020. It is currently approved for several indications involving metastatic or unresectable cancers that have not responded to previous treatments.

Approved Indications

The FDA has approved Trodelvy for the following uses:

• Triple-Negative Breast Cancer (TNBC): For adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of which was for metastatic disease.
• HR-Positive, HER2-Negative Breast Cancer: For adult patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
• Urothelial Cancer: For adult patients with locally advanced or metastatic urothelial cancer who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. This indication was granted under accelerated approval based on tumor response rate and duration of response.

Boxed Warning

Trodelvy carries a boxed warning, the most serious safety notification required by the FDA, for two specific risks:

• Severe Neutropenia: The medication can cause a severe drop in white blood cell counts (neutropenia), which can lead to serious infections. Healthcare providers monitor blood counts before each dose and may delay or reduce the dosage if levels are too low.
• Severe Diarrhea: Treatment can cause severe diarrhea, which may lead to dehydration. Patients are advised to start antidiarrheal medication and contact their doctor at the first sign of loose stools.

Trodelvy is a specialty medication administered as an intravenous (IV) infusion by a healthcare professional. Because it is given in a clinical setting rather than purchased at a retail pharmacy, the total cost typically includes the price of the drug as well as fees for the infusion procedure and medical supplies.

Several factors can influence the final cost of treatment:

• Insurance coverage: Most private insurance plans and Medicare cover Trodelvy, but your out-of-pocket expenses will depend on your plan's specific deductibles, copays, or coinsurance.
• Treatment location: Costs may vary depending on whether the infusion is administered in a hospital, an outpatient clinic, or a private doctor's office.
• Dosage: The amount of medication prescribed is based on your body weight, which directly impacts the cost per treatment cycle.

Financial assistance or patient support programs may be available through the manufacturer for those who qualify. It is recommended to contact your insurance provider or the billing department at your treatment facility for a detailed estimate of your expected costs.