Enfortumab Vedotin (Padcev): Nectin-4-Targeted ADC for Advanced Urothelial Carcinoma

　　Drug Overview

　　Enfortumab vedotin-ejfv(brand name:Padcev)is an antibody-drug conjugate(ADC)targeting Nectin-4,approved by the U.S.FDA in 2019.The drug consists of a monoclonal antibody directed against Nectin-4 conjugated to the microtubule inhibitor monomethyl auristatin E(MMAE).It specifically binds to Nectin-4,which is highly expressed on the surface of tumor cells,and precisely delivers the cytotoxic agent inside tumor cells,effectively inhibiting tumor cell division and inducing apoptosis.

　　Indications

　　Combination Therapy(with Pembrolizumab)

　　Enfortumab vedotin in combination with pembrolizumab is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma,regardless of cisplatin eligibility.

　　Monotherapy

　　Indicated for adult patients with locally advanced or metastatic urothelial carcinoma who:

　　Have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy

　　Are ineligible for cisplatin-containing chemotherapy and have received one or more prior lines of systemic therapy

　　Dosage and Administration

　　Recommended Dosage

　　In combination with pembrolizumab:1.25 mg/kg(maximum 125 mg per dose)administered as an intravenous infusion on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

　　As monotherapy:1.25 mg/kg(maximum 125 mg per dose)administered as an intravenous infusion on Days 1,8,and 15 of each 28-day cycle until disease progression or unacceptable toxicity.

　　Administration

　　This product is for intravenous infusion only,with an infusion time of 30 minutes.Do not administer as an intravenous push or bolus injection.

　　Adverse Reactions

　　Common Adverse Reactions with Combination Therapy(Pembrolizumab)

　　Laboratory abnormalities include:increased aspartate aminotransferase,increased creatinine,increased glucose,increased lipase,lymphopenia,increased alanine aminotransferase,decreased hemoglobin,decreased sodium,decreased phosphorus,decreased albumin,increased uric acid,neutropenia,decreased potassium,and thrombocytopenia.

　　Clinical symptoms include:rash,fatigue,peripheral neuropathy,pruritus,diarrhea,alopecia,weight loss,decreased appetite,dry eye,nausea,constipation,dysgeusia,and urinary tract infection.

　　Common Adverse Reactions with Monotherapy

　　Laboratory abnormalities include:increased glucose,increased aspartate aminotransferase,lymphopenia,increased creatinine,decreased albumin,decreased hemoglobin,decreased sodium,increased alanine aminotransferase,decreased phosphorus,neutropenia,increased uric acid,increased lipase,and thrombocytopenia.

　　Clinical symptoms include:rash,fatigue,peripheral neuropathy,alopecia,decreased appetite,diarrhea,nausea,pruritus,dry eye,dysgeusia,constipation,weight loss,abdominal pain,and dry skin.

　　Serious Adverse Reactions

　　Cutaneous reactions:including Stevens-Johnson syndrome(SJS)and toxic epidermal necrolysis(TEN),which can be fatal and most often occur during the first treatment cycle.

　　Hyperglycemia and diabetic ketoacidosis:can occur in patients with or without a history of diabetes and may be fatal.

　　Pneumonitis and interstitial lung disease(ILD):severe cases can be fatal.

　　Peripheral neuropathy:occurs in up to 67%of patients receiving combination therapy,and some cases are irreversible.

　　Ocular disorders:primarily manifest as dry eye and blurred vision.

　　Precautions

　　Severe Cutaneous Reactions

　　This product can cause severe and potentially fatal cutaneous adverse reactions.If SJS/TEN is suspected or a severe cutaneous reaction occurs,discontinue treatment immediately and refer the patient to a dermatologist.Permanently discontinue Padcev in patients with confirmed SJS/TEN,Grade 4 cutaneous reactions,or recurrent Grade 3 cutaneous reactions.

　　Hyperglycemia

　　Closely monitor blood glucose levels in all patients during treatment.Interrupt treatment when blood glucose exceeds 250 mg/dL and resume only after glucose is controlled.

　　Pneumonitis and Interstitial Lung Disease

　　Monitor patients for signs and symptoms of pneumonitis or ILD,including cough,dyspnea,and hypoxia.Interrupt treatment for Grade 2 pneumonitis/ILD and consider dose reduction upon resolution.Permanently discontinue Padcev in patients with Grade 3 or 4 pneumonitis/ILD.

　　Peripheral Neuropathy

　　Closely monitor patients for new or worsening neurological symptoms such as numbness,tingling,burning sensation,and muscle weakness.Permanently discontinue Padcev in patients with Grade 3 or higher peripheral neuropathy.

　　Ocular Disorders

　　Advise all patients to use artificial tears routinely during treatment to prevent dry eye.Perform ophthalmologic evaluation if ocular symptoms develop,and topical corticosteroids may be considered if necessary.

　　Infusion Site Extravasation

　　Ensure proper venous access before infusion and closely monitor the infusion site for signs of extravasation such as redness and pain during administration.If extravasation is suspected,stop the infusion immediately and institute appropriate management.

　　Embryo-Fetal Toxicity

　　This product can cause fetal harm.Advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose.Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose.

　　Hepatic Impairment

　　Avoid use of Padcev in patients with moderate or severe hepatic impairment,defined as total bilirubin>1.5 times the upper limit of normal with any aspartate aminotransferase level.

　　Contraindications

　　Absolute contraindications for enfortumab vedotin are currently not established.