Enfortumab vedotin

UK SPC (Padcev 20 mg powder for concentrate for solution for infusion, https://www.medicines.org.uk/emc/product/13669/smpc). Treatment should be initiated and supervised by a physician experienced in the use of anti-cancer therapies; ensure good venous access before starting. INDICATION-SPECIFIC SCHEDULES: (a) with pembrolizumab for neoadjuvant and adjuvant treatment of muscle-invasive bladder cancer - neoadjuvant on Days 1 and 8 of each 21-day cycle for 3 cycles or until disease progression precluding radical cystectomy or unacceptable toxicity, then adjuvant on Days 1 and 8 of each 21-day cycle for 6 cycles or until disease recurrence or unacceptable toxicity; (b) with pembrolizumab for unresectable or metastatic urothelial cancer - Days 1 and 8 of every 21-day cycle until disease progression or unacceptable toxicity; (c) as monotherapy for locally advanced or metastatic urothelial cancer - Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Pembrolizumab is given as either 200 mg every 3 weeks or 400 mg every 6 weeks by IV infusion over 30 minutes, and should be administered AFTER enfortumab vedotin when given on the same day (refer to the pembrolizumab SmPC). DOSE REDUCTION SCHEDULE: starting 1.25 mg/kg up to 125 mg -> first reduction 1.0 mg/kg up to 100 mg -> second reduction 0.75 mg/kg up to 75 mg -> third reduction 0.5 mg/kg up to 50 mg. DOSE MODIFICATIONS: suspected Stevens-Johnson syndrome or toxic epidermal necrolysis or bullous lesions - withhold immediately and refer to specialised care; confirmed SJS/TEN, Grade 4 or recurrent Grade 3 skin reactions - permanently discontinue; Grade 2 worsening, Grade 2 with fever, or Grade 3 skin reaction - withhold until Grade <=1, consider referral to specialised care, resume at the same dose level or consider reduction by one dose level. Hyperglycaemia with blood glucose >13.9 mmol/L (>250 mg/dL) - withhold until improved to <=13.9 mmol/L (<=250 mg/dL) then resume at the same dose level. Pneumonitis/interstitial lung disease Grade 2 - withhold until Grade <=1 then resume at the same dose or one dose level lower; Grade >=3 - permanently discontinue. Peripheral neuropathy Grade 2 - withhold until Grade <=1, resume at the same dose level for a first occurrence, or reduced by one dose level on recurrence; Grade >=3 - permanently discontinue. Elderly: no dose adjustment in patients aged 65 years and over. Hepatic impairment: no dose adjustment in mild impairment (total bilirubin 1 to 1.5x ULN with any AST, or total bilirubin <=ULN with AST >ULN); evaluated in only a limited number of patients with moderate and severe hepatic impairment, which is expected to increase systemic exposure to MMAE - monitor closely, no specific dose recommendation can be given. PAEDIATRIC: there is no relevant use of enfortumab vedotin in the paediatric population for locally advanced or metastatic urothelial cancer or muscle-invasive bladder cancer (UK SPC); US labelling states safety and effectiveness in paediatric patients have not been established. Any under-18 use must be verified against a children's formulary and specialist paediatric oncology protocol.