Enfortumab Vedotin-ejfv (Padcev)

How is the drug name pronounced?

Enfortumab Vedotin: En-fort-TU-mu-MAB ved-AUGHT-in

Padcev: PAD-sev


What cancer(s) does this drug treat?

Bladder and urinary tract cancer

Padcev is approved for:

  • Patients with bladder and urinary tract cancer (urothelial cancer) that has spread to other parts of the body and cannot be removed by surgery, and who have previously received a PD-1 or PD-L1 inhibitor, and a platinum-containing chemotherapy.

Limitations of Use

Age: The safety and efficacy of Padcev has not been established in patients under 18 years of age.
Fertility/Pregnancy/breastfeeding: Padcev may impair fertility in men. Padcev can cause harm to the fetus, and is not recommended for use during pregnancy. Women should not start Padcev treatment when pregnant. Women are advised to use contraception during treatment with Padcev and for at least 2 months after the last dose of Padcev. Men are advised to use contraception during treatment with Padcev and for at least 4 months after the last dose of Padcev. The risks associated with Padcev during breastfeeding are not known and cannot be ruled out. Due to the potential for serious adverse reactions in the breastfed child, women are advised not to breastfeed during treatment with Padcev and for up to 3 weeks after the last dose of Padcev.
Exclusions: Padcev is not recommended for patients with moderate to severe liver disease.
Interactions with other drugs: Patients who are treated with medications called strong CYP3A4 inhibitors during Padcev treatment should be closely monitored for signs of adverse reactions.


What type of immunotherapy is this?

Antibody therapy

  • Antibody–drug conjugate

How does this drug work?

Target:

  • Nectin-4 

Padcev is an antibody–drug conjugate that was made in the laboratory by joining a small, highly potent chemotherapy to a large antibody molecule. The antibody delivers the chemotherapy drug to a cancer cell, reducing the effects of the chemotherapy drug on most other cells of the body.

Antibody molecules are proteins that can bind tightly to a particular target molecule. Antibodies have an overall “Y” shape. The two tips of the upper arms of the “Y” shape are the parts of the antibody that can very precisely bind to their targets. The target molecule that the antibody in Padcev binds to is Nectin-4, a molecule that is found in high amounts on the surface of urothelial cancer cells.

The chemotherapy drug Monomethyl auristatin E (MMAE) is joined to the stem of the antibody’s “Y” shape. There are about 4 MMAE molecules bound to every antibody molecule in Padcev. MMAE is not toxic when it is joined to the antibody, and needs to be released in order to become active.

When Padcev binds to Nectin-4 on the surface of cancer cells, it can enter the cell it is bound to. Inside the cell, the chemotherapy part of Padcev is released and becomes activated. MMAE prevents the cancer cells from multiplying and leads to their death.

Because Nectin-4 is also present on healthy cells of the urethra and bladder and on some other cell types, Padcev may attack these cells and cause unwanted effects, in addition to killing cancer cells.

Illustration showing how Padcev works


How is this drug given to the patient?

Padcev is administered via a tube in the vein (intravenous infusion, or I.V.) over 30 minutes once a week for 3 weeks on days 1, 8 and 15, followed by 13 days with no treatment. Each 28-day (4-week) period is one “treatment cycle”. The number of treatment cycles the patient receives is determined by their healthcare provider, and is based on the response to treatment.

Image showing the method of administration for Padcev


What are the observed clinical results?

It is important to keep in mind that each patient’s actual outcome is individual and may be different from the results found in the clinical studies. In addition, with immunotherapy, sometimes it takes several months for responses to be observed.

Bladder and urinary tract cancer

In a clinical trial, 125 patients with bladder and urinary tract cancer (urothelial cancer) that has spread to other parts of the body and cannot be removed by surgery, and who have previously received a PD-1 or PD-L1 inhibitor, and a platinum-containing chemotherapy, were treated with Padcev.

At a median follow-up of 10 months, 44% of patients had their tumors shrink, including 12% of patients whose cancer disappeared entirely. Patients who responded to treatment continued to respond for a median of 8 months.


What are the side effects?

The most common side effects of Padcev include nausea, vomiting, diarrhea, changes in sense of taste, fatigue, decreased appetite, hair loss, dry eyes and skin, rash, numbness or tingling in the hands or feet, and muscular weakness.

Other potential side effects of Padcev treatment include high blood sugar, blurred vision, and leakage of Padcev from the vein it was administered to into the surrounding tissue. Patients should immediately report burning, pain, stinging, redness, or swelling around the injection or infusion site to their healthcare provider.

Patients should immediately report any symptoms to their healthcare provider, who can then initiate actions to limit or reverse the side effects. For a more complete list of possible side effects, see the full prescribing information.


Additional Information

Manufacturer

Astellas Pharma and Seattle Genetics

Approval

FDA


Understanding Cancer Immunotherapy Research

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