Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a targeted cancer treatment called an antibody-drug conjugate (ADC) used to treat certain types of triple-negative breast cancer (TNBC) and hormone receptor-positive, HER2-negative breast cancer. It is used in cancer that is either locally advanced, has spread to other parts of the body (metastatic) and cannot be removed with surgery. Trodelvy may be used on its own or combined with other cancer treatments.

Trodelvy is an antibody-drug conjugate, which is a targeting antibody linked with a chemotherapy drug. The antibody seeks out and attaches to Trop-2, a protein common on cancer cells, then releases the chemotherapy component (SN-38) into the cell to kill it while largely sparing healthy tissue.

Trodelvy is administered as an intravenous (IV) infusion, usually on Days 1 and 8 of a continuous 21-day cycle. The first infusion takes about three hours, while subsequent well-tolerated doses may take one to two hours. Infusions are administered in a hospital or infusion clinic by a healthcare professional.

Trodelvy is FDA-approved to be used for specific types of locally advanced or metastatic triple-negative breast cancer (mTNBC) and locally advanced or metastatic HR-Positive, HER2-Negative breast cancer.

Triple-negative breast cancer (TNBC), unresectable locally advanced or metastatic as a:

• First line therapy, as a single agent, for adults who aren't candidates for a PD-1 or PD-L1 inhibitor-based therapy.
• First line therapy, combined with pembrolizumab (or the pembrolizumab plus berahyaluronidase alfa-pmph), for adults whose tumors express PD-L1 at a CPS of 10 or higher, confirmed by an FDA-authorized test.
• Second line or later therapy, for adults who have had two or more prior systemic therapies, with at least one given for metastatic disease.

HR-positive, HER2-negative breast cancer, unresectable locally advanced or metastatic (HER2 defined as IHC 0, IHC 1+, or IHC 2+/ISH-negative in adults:

• That have already had endocrine-based therapy plus at least two more systemic therapies in the metastatic setting.

Trodelvy is an antibody-drug conjugate, a type of treatment that combines two parts into a single medicine: a targeting antibody and a chemotherapy drug. The two parts work together so the chemotherapy can be delivered more precisely to cancer cells.

The antibody part (called sacituzumab) seeks out and attaches to Trop-2, a protein found on the surface of many cancer cells, including breast cancer cells. Once it attaches, the medicine is drawn inside the cancer cell, where it releases its chemotherapy component, called SN-38.

SN-38 is a topoisomerase I inhibitor. It blocks an enzyme (topoisomerase I) that cancer cells rely on to repair breaks in their DNA as they grow and divide. By preventing this repair, SN-38 causes DNA damage that the cell cannot fix, which triggers the cancer cell to die. Because the antibody helps concentrate the chemotherapy at the cancer cells, this targeted approach is designed to limit how much reaches healthy tissue.

Your healthcare provider will give Trodelvy into your vein through an intravenous (IV) line, the infusion will initially be given over 3 hours. If you tolerate the first dose well, future doses may be given over 1 to 2 hours.

• Trodelvy is given 1 time each week, on Day 1 and Day 8 of a 21-day treatment cycle.
• Before each dose, you will receive medicines to help prevent infusion reactions and nausea and vomiting.
• You will be monitored for side effects during and for at least 30 minutes after you receive each infusion of this medication.
• Your healthcare provider may slow down or temporarily stop your infusion if you have an infusion-related reaction, or permanently stop this medication if you have a life-threatening infusion-related reaction.

This medicine commonly causes diarrhea. Severe diarrhea can lead to dehydration, which may require medical treatment. Tell your doctor right away the first time you have diarrhea while receiving this medicine.

You may get infections more easily, even serious or fatal infections. You may need frequent medical tests, and your cancer treatments may be delayed based on the results.

You will usually stay on Trodelvy until your disease progresses or side effects or toxicity become unacceptable. How long you continue treatment with this medicine is often decided after conversations between the doctor and the patient.

Trodelvy has a boxed warning for severe, life-threatening, or fatal neutropenia and for severe diarrhea. A boxed warning is the strongest safety-related warning issued by the FDA.

Low white blood cell count (neutropenia)

A low white blood cell count can become severe and lead to infections that may be life-threatening or cause death, sometimes as early as the first cycle of treatment. Your healthcare provider should check your blood cell counts during treatment. If you have an increased risk of developing a low white blood cell count with a fever (febrile neutropenia), your provider may give you a medicine called G-CSF (granulocyte colony-stimulating factor) starting in the first cycle to help prevent it.

Tell your healthcare provider right away if you develop any of these signs of infection during treatment:

• fever
• chills
• cough
• shortness of breath
• burning or pain when you urinate

Severe diarrhea

Severe diarrhea can cause you to lose too much body fluid (dehydration) and can lead to kidney problems. Your healthcare provider should monitor you for diarrhea and give you medicine as needed to help control it. If you lose too much fluid, your provider may give you fluids and electrolytes to replace lost body salts. If you develop diarrhea during treatment, your provider should check whether it may be caused by an infection.

Tell your healthcare provider right away if:

• you get diarrhea for the first time during treatment
• you develop black or bloody stools
• you develop signs of losing too much fluid and body salts, such as lightheadedness, dizziness, or faintness
• you cannot take fluids by mouth because of nausea or vomiting
• you cannot get your diarrhea under control within 24 hours

Other serious warnings include:

Serious hypersensitivity and infusion-related reactions, including anaphylaxis, can occur with Trodelvy. Do not receive this infusion if you have had a severe allergic reaction to the active ingredient sacituzumab govitecan-hziy or any of the inactive ingredients in the injection. There is a full list of ingredients at the bottom of this document. Your healthcare provider should monitor you during each infusion and for at least 30 minutes after each infusion, and will permanently stop Trodelvy if you have a severe (Grade 4) infusion-related reaction.

Nausea and vomiting. This medicine may cause nausea and vomiting, which can be severe. Your healthcare provider should prescribe antiemetic preventive treatment and withhold Trodelvy for patients with Grade 3 nausea or Grade 3-4 vomiting at the time of treatment.

Genetic variations in the UGT1A1 gene. Patients with gene variations in the UGT1A1 gene are at increased risk of side effects of Trodelvy, such as low blood cell counts including neutropenia (low levels of neutrophils, a type of white blood cell), febrile neutropenia, and anemia (low levels of red blood cells).

Fetal harm. Trodelvy can harm an unborn baby. Women using Trodelvy who are of childbearing potential should use effective contraception during treatment and for 6 months after the last dose. Because of a potential risk of genetic damage, males using Trodelvy with a female partner who can become pregnant should use effective birth control during treatment and for 3 months after the last dose.

It is not known if Trodelvy is safe and effective in people with moderate or severe liver problems or in children.

You should not be treated with Trodelvy if you have ever had a severe allergic reaction to it.

Before taking this medicine, tell your doctor if you have ever had:

• liver disease; or
• you've been told that you carry a gene called UGT1A1*28, which may increase your risk of getting infections while using this medicine.

Pregnancy

Trodelvy can harm an unborn baby. Your healthcare provider should check whether you are pregnant before you start treatment.

If you are a woman who can become pregnant, use effective birth control during treatment and for at least 6 months after your last dose. Tell your doctor right away if a pregnancy occurs.

Because of a potential risk of genetic damage, if you are a man with a partner who can become pregnant, use effective birth control during treatment and for at least 3 months after your last dose.

Trodelvy may also make it harder to become pregnant (impaired fertility). You should still use birth control to prevent pregnancy during treatment, because the medicine can harm an unborn baby.

Breastfeeding

Do not breastfeed while using this medicine, and for at least 1 month after your last dose.

Common Trodelvy side effects

When Trodelvy is used alone, the most common side effects include:

• decreased white blood cell counts
• decreased red blood cell counts
• nausea
• diarrhea
• feeling tired or weak
• hair loss
• increased blood sugar (glucose) levels
• constipation
• vomiting
• decreased blood protein (albumin) levels
• increased alkaline phosphatase levels in the blood
• decreased appetite
• stomach pain
• decreased creatinine clearance (a measure of kidney function)
• decreased magnesium and potassium levels in the blood

When Trodelvy is used with pembrolizumab, the most common side effects include:

• decreased white blood cell counts
• decreased red blood cell counts
• diarrhea
• nausea
• feeling tired or weak
• hair loss
• increased alkaline phosphatase levels in the blood
• increased blood sugar (glucose) levels
• increased liver enzyme levels in the blood
• constipation
• rash
• decreased potassium levels in the blood
• increased lactate dehydrogenase levels in the blood
• vomiting
• stomach pain
• headache
• increased eosinophil levels in the blood (a type of white blood cell)
• decreased blood protein (albumin) levels

Doses may be delayed, reduced, or stopped if side effects are severe.

Serious Trodelvy side effects

This medicine can cause severe or life-threatening allergic reactions.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection or within 24 hours afterward. Tell your medical caregivers if you feel dizzy, light-headed, itchy, sweaty, or have a fever, chills, trouble breathing, or swelling in your face or throat.

You may get infections more easily, even serious or fatal infections. Call your doctor right away if you have signs of infection, such as:

• pain or burning when you urinate;
• low red blood cells (anemia) - pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet; or
• low white blood cell counts - fever, mouth sores, skin sores, sore throat, cough, trouble breathing.

Trodelvy can cause severe diarrhea. Tell your doctor right away if you have:

• diarrhea (the first time it occurs);
• diarrhea lasting longer than 24 hours (even if you use anti-diarrhea medicine);
• black or bloody stools;
• severe or ongoing vomiting, especially if you can't keep liquids down; or
• a light-headed feeling, like you might pass out.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual adult Trodelvy dose for breast cancer

Dose: 10 mg/kg given as an intravenous (IV) infusion once a week on Days 1 and 8 of each 21-day treatment cycle.

Maximum dose: 10 mg/kg per dose. Trodelvy should not be given at doses higher than 10 mg/kg.

Duration of therapy: Treatment continues until the disease worsens (disease progression) or side effects become unacceptable.

When Trodelvy is combined with pembrolizumab

The Trodelvy dose is the same, 10 mg/kg on Days 1 and 8 of each 21-day cycle. When Trodelvy is given with pembrolizumab (or pembrolizumab and berahyaluronidase alfa-pmph), the pembrolizumab is stopped after about 24 months. Refer to the pembrolizumab prescribing information for its own dosing.

Dose modifications

Because of side effects, your healthcare provider may reduce your dose. The first reduction is to 7.5 mg/kg, and a second reduction, if needed, is to 5 mg/kg. If you cannot tolerate the 5 mg/kg dose, treatment is stopped permanently. Once your dose has been lowered for side effects, it is not raised again.

Medicines given before each dose (premedication)

Before each infusion, your healthcare provider should give you medicines to help prevent infusion reactions and to help prevent nausea and vomiting. If you are at increased risk of a low white blood cell count with fever (febrile neutropenia), you may also be given G-CSF (granulocyte colony-stimulating factor) starting in the first cycle to help prevent it.

How Trodelvy is given

Trodelvy is given as an IV infusion. The first infusion is given over 3 hours. If earlier infusions were tolerated, later infusions are given over 1 to 2 hours. Your healthcare provider will monitor you during each infusion and for at least 30 minutes after it finishes.

Important

Trodelvy should not be substituted for, or used with, other medicines that contain irinotecan or its active form SN-38.

Call your doctor for instructions if you miss an appointment for your infusion.

In a medical setting, an overdose would be treated quickly.

How effective is Trodelvy for triple-negative breast cancer (mTNBC)?

mTNBC Trodelvy patients had:

• increased progression-free survival (5.6 vs. 1.7 months)
• increased overall survival (12.1 vs. 6.7 months)
• better tumour response, how many people’s tumours shrank (35% vs 5%)

These results are from the phase III ASCENT trial (NCT02574455). The trial involved patients with relapsed or refractory metastatic triple-negative breast cancer, whose cancer had not spread to the brain, and compared patients treated with Trodelvy to patients treated with the physician’s choice of single-agent chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine).

How effective is Trodelvy for pre-treated HR+/HER2- metastatic breast cancer?

HR+/HER2- metastatic breast cancer, Trodelvy patients had:

• Overall survival (OS) benefit of 3.2 months (14.4 months Trodelvy vs. 11.2 months chemotherapy)
• 34% reduction in risk of disease progression or death (median PFS: 5.5 versus 4.0 months)
• Three times more Trodelvy patients were progression-free at one year (21% versus 7%).

These results are from the TROPiCS-02 study (NCT03901339), which involved patients with relapsed or refractory HR+/HER2- metastatic breast cancer comparing Trodelvy treatment vs. single-agent chemotherapy (treatment of the physician’s choice). Patients had to have previously received other specified therapies.

Trodelvy cost will depend on your insurance plan and the pharmacy you use.

A Trodelvy coupon or Trodelvy savings card may be available which you could be eligible for. Ask your doctor or pharmacist if you qualify, or view the Trodelvy coupons and price guide page.

Trodelvy J code is J9317 (sacituzumab govitecan-hziy, 2.5 mg).J codes are used for medicines that are not taken orally and include injections, inhalations, and chemotherapies. Your physician will need the J code when filling out forms for your treatment.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain medicines may affect the way Trodelvy works.

• Concomitant administration of UGT1A1 inhibitors such as flunitrazepam or propofol may increase the incidence of side effects due to a potential increase in systemic exposure to SN-38. Avoid co-administration.
• Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 Inducers such as phenytoin and phenobarbital. Avoid co-administration.

This list is not complete. Many other drugs may interact with this medicine including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

HCPs and patients often use the Trodelvy Prescribing Information (PI) for more detailed information about this medicine. The Package Insert contains more comprehensive information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interaction, and more. Discuss any medical questions you have with your HCP (health care professional). This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The Package Insert is sometimes called Trodelvy Prescribing Information (PI) or FDA label.

Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect them from light until the time of reconstitution. Do not freeze.

Trodelvy is a hazardous drug. Follow applicable special handling and disposal procedures.

Active ingredient: sacituzumab govitecan-hziy

Inactive ingredients: 2-(N-morpholino) ethane sulfonic acid (MES), polysorbate 80, and trehalose dihydrate