FDA approved Padcev (enfortumab vedotin) for Muscle Invasive Bladder CancerFDA approved Padcev combination for bladder cancer before and after surgery

Padcev is a Nectin-4-directed antibody and microtubule inhibitor conjugate. It binds to Nectin-4 on cancer cells and delivers the microtubule-disrupting agent monomethyl auristatin E (MMAE), leading to cell cycle arrest and apoptosis.

Padcev in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph is indicated as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment for adult patients with MIBC who are ineligible for cisplatin-containing chemotherapy. The combination is also indicated for adult patients with locally advanced or metastatic urothelial cancer (mUC). As a single agent, Padcev is indicated for adult patients with locally advanced or mUC who have previously received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy, or who are ineligible for cisplatin-containing chemotherapy and have received one or more prior lines of therapy.

For MIBC (neoadjuvant and adjuvant): The recommended dose is 1.25 mg/kg (up to a maximum of 125 mg for patients ≥100 kg) as an intravenous infusion over 30 minutes on Days 1 and 8 of a 21-day cycle. Neoadjuvant: 3 cycles or until disease progression that precludes curative intent cystectomy or unacceptable toxicity. Adjuvant: 6 cycles or until disease recurrence or unacceptable toxicity. For mUC (combination): Same dose on Days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity. For mUC (single agent): 1.25 mg/kg (up to 125 mg) on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Administer Padcev prior to pembrolizumab if on the same day. Avoid use in patients with moderate or severe hepatic impairment.

Trial data not available in label.

Boxed warning: Serious skin reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have occurred. For persistent or recurrent Grade 2 skin reactions, consider withholding until Grade ≤1, then resume at same or reduced dose. For Grade 3, withhold until Grade ≤1, then resume at same or reduced dose. Suspected SJS/TEN: immediately withhold and consult specialist. Confirmed SJS/TEN, Grade 4, or recurrent Grade 3: permanently discontinue. Hyperglycemia: monitor blood glucose. Other warnings include peripheral neuropathy, ocular disorders, pneumonitis, and infusion site extravasation.

Padcev provides a targeted therapy option for MIBC patients ineligible for cisplatin, both in neoadjuvant/adjuvant setting and for advanced disease. It is also a treatment option for mUC after prior immunotherapy and chemotherapy, or for cisplatin-ineligible patients with prior therapy.