Medicinal product for the treatment of urothelial cancers in adults

About the medicinal product

Padcev contains the active substance enfortumab vedotin and is used for the treatment of adults with locally advanced or metastatic urothelial cancer (mUC)^[1]. Patients who are eligible for this treatment must have previously received platinum-containing chemotherapy and suffered a progression or relapse of the disease during or after treatment with immune checkpoint inhibitors (PD-1/PD-L1^[2]).

^[1] _{Metastatic urothelial cancer (mUC): urothelial cancer refers to bladder cancer and cancers of the urinary tract (renal pelvis, ureter or urethra).}

^[2] _{PD-1/ PD-L1: Cancer drugs that act as inhibitors of the programmed cell death receptor 1 (PD-1) or the programmed cell death ligand 1 (PD-L1).}

Mode of action

Enfortumab vedotin belongs to the class of antibody-drug conjugates (ADCs). The active substance consists of a monoclonal antibody (immunologically active protein) linked to the substance monomethyl auristatin E (MMAE). MMAE is a cytotoxin (cell poison) with the ability to kill cancer cells. The monoclonal antibody binds predominantly to a specific receptor (target site) on the surface of the urothelial cancer cells, causing MMAE to be released into the cells. The resulting initiated process leads to the death of the cancer cell.

Use

Padcev is a prescription-only medicine and is authorised as a powder for concentrate for solution for infusion. It is administered as a fluid into the veins. The vials contain 20 mg or 30 mg of enfortumab vedotin.

The recommended dose is 1.25 mg/kg body weight, up to a maximum of 125 mg, and is administered over 30 minutes on days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable side effects.

Efficacy

The efficacy of Padcev in the treatment of urothelial cancers was investigated mainly in study EV-301 with a total of 608 participants. The patients had locally advanced or metastatic urothelial cancer and had previously been treated with a platinum-containing chemotherapy and suffered a relapse or progression of the disease during or after treatment with immune checkpoint inhibitors (PD-1/PD-L1 inhibitor).

To confirm the efficacy of Padcev, half of the patients were treated with Padcev and the other half with a chemotherapy determined by the study doctor.

The study showed a statistically significant improvement in the overall survival^[3], progression-free survival^[4] and objective response rate^[5] of those patients who were treated with Padcev compared to those who received the chemotherapy.

^[3] _{Overall survival: The overall survival refers to the period between the start of treatment and the death of the patient.}

^[4] _{Progression-free survival (PFS): period between the start of a treatment or a clinical trial and the onset of disease progression or the death of the patient.}

^[5] _{Objective response rate (ORR): The objective response rate describes the percentage of patients with a clinically relevant reduction in tumour size}

Precautions, undesirable effects & risks

Padcev must not be used in those who are hypersensitive to the active substance or any of the excipients.

The most frequent undesirable effects observed in all patients treated with Padcev were alopecia (excessive hair loss), fatigue, decreased appetite, peripheral sensory neuropathy (disorder of the nervous system), diarrhoea, nausea, pruritus (itching), dysgeusia (impaired taste), anaemia, weight loss, maculopapular (nodular and spotty) rash, dry skin, vomiting, increased AST/ALT^[6], hyperglycaemia (excessively high blood sugar), dry eye and rash.

Padcev can cause other serious side effects, and these must be reported to a doctor immediately (e.g. serious adverse skin reactions, acute kidney injury, lung inflammation, urinary tract infection and sepsis).

All precautions, risks and other possible undesirable effects are listed in the Information for healthcare professionals.

^[6] _{AST/ALT: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): these are both enzymes produced mainly in the liver. Elevated levels of activity of these enzymes in the blood may indicate liver-related diseases.}

Why the medicinal product has been authorised

Patients with urothelial cancer that progresses after a platinum-based chemotherapy and subsequent treatment with immune checkpoint inhibitors (PD-1/ PD-L1 inhibitor) have a poor prognosis and limited options for further treatment.

The pivotal study showed a statistically and clinically significant benefit for Padcev compared to the control group, with a prolongation of median^[7] overall survival of 3.9 months

Based on all the available data, the benefits of Padcev outweigh the risks. Swissmedic has therefore authorised the medicinal product Padcev for the treatment of adults with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and suffered disease progression or relapse during or after treatment with immune checkpoint inhibitors (PD-1/ PD-L1).

^[7] _{Median: The value that lies exactly in the middle of a distribution of data is called the median or central value. Half of the data values are always smaller than the median, the other half are always greater.}

Further information on the medicinal product

Information for healthcare professionals:

Healthcare professionals can answer any further questions.

^{The date of revision of this text corresponds to that of the SwissPAR. New information concerning the authorised medicinal product in question will not be incorporated into the Public Summary SwissPAR.}

^{Swissmedic monitors medicinal products authorised in Switzerland. Swissmedic initiates the necessary action in the event of newly discovered adverse drug reactions or other safety-relevant signals.}

^{New findings that could impair the quality, efficacy or safety of this medicinal product are recorded and published by Swissmedic. If necessary, the medicinal product information is adapted.}