PADCEV

What it is

PADCEV (enfortumab vedotin) is a Nectin-4 targeted antibody drug conjugate (ADC) comprised of a fully human IgG1 kappa antibody, conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable vc maleimidocaproyl linker. Each vial of powder for concentrate for infusion contains either 20 mg or 30 mg enfortumab vedotin.

Approved indications

— PADCEV in combination with pembrolizumab, for the first-line treatment of adult patients with locally advanced or metastatic urothelial cancer. — PADCEV as monotherapy, for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and a programmed death receptor-1 or programmed death-ligand-1 inhibitor.

Dosing overview

Key safety warnings

PADCEV can cause severe and fatal cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). Withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; Grade 4 or recurrent Grade 3 skin reactions. Hyperglycaemia and diabetic ketoacidosis (DKA) including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Hyperglycaemia occurred more frequently in patients with pre-existing hyperglycaemia or a high body mass index (≥30 kg/m²). Blood glucose levels should be monitored regularly in patients with or at risk for diabetes mellitus or hyperglycaemia. If blood glucose is elevated (>13.9 mmol/L; >250 mg/dL), withhold PADCEV. Severe, life-threatening or fatal pneumonitis/interstitial lung disease occurred in patients treated with PADCEV. The incidence of pneumonitis/interstitial lung disease, including severe events occurred at a higher rate when PADCEV was given in combination with pembrolizumab compared to PADCEV as monotherapy. Peripheral neuropathy, predominantly sensory, has occurred with PADCEV, including Grade ≥3 reactions. Monitor patients for symptoms of new or worsening peripheral neuropathy as these patients may require a delay, dose reduction or discontinuation of PADCEV.

Contraindications

PADCEV is contraindicated in patients with known hypersensitivity to enfortumab vedotin or to any of the excipients in the formulation.

PBS listing

PADCEV powder for intravenous infusion 20 mg is listed on the PBS with streamlined authority required restriction and an ex-manufacturer price of A$942.06.

Regulatory history

PADCEV enfortumab vedotin 20 mg and 30 mg powder for injection vials were first listed on the ARTG on 7 July 2022. The TGA approved PADCEV on 30 June 2022 for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. PADCEV is subject to additional monitoring in Australia. This will allow quick identification of new safety information. The PBAC recommended this monotherapy indication in March 2022 but did not recommend it. The PBAC then deferred its recommendation in November 2022. In November 2024, the PBAC recommended PADCEV for locally advanced or metastatic urothelial cancer as a streamlined Section 100 listing, determining it to be cost-effective at A$55,000 to less than A$75,000 per QALY gained with a risk sharing arrangement.