PADCEV (enfortumab védotine) - Cancer urothélial

Key points

Approval of reimbursement as monotherapy for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma, who have previously received chemotherapy based on platinum salts and a programmed death receptor-1 inhibitor (anti-PD-1) or a programmed death receptor ligand-1 inhibitor (anti-PD-L1).

Therapeutic improvement?

Therapeutic improvement in the therapeutic strategy for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma, who have previously received chemotherapy based on platinum salts and an anti-PD-1 drug or an anti-PD-L1 drug.

Role in therapeutic strategy?

As a first-line approach, treatment is based on polychemotherapy based on platinum salts. For patients eligible for cisplatin (creatinine clearance > 60 ml/min, ECOG 0 or 1), the GC (gemcitabine, cisplatin), MVAC-HD (methotrexate, vinblastine, adriamycin and cisplatin), MVAC or PCG (paclitaxel, cisplatin, gemcitabine) regimens may be used.

For patients ineligible for cisplatin, chemotherapy based on carboplatin is recommended (particularly carboplatin + gemcitabine). For patients ineligible for cisplatin with PD-L1 marker + tumour expression, atezolizumab (anti-PD-L1) and pembrolizumab (anti-PD1) have been granted a marketing authorisation, but are not covered for this indication in France.

Note that, for patients whose disease has not progressed after platinum-based chemotherapy, the use of BAVENCIO (avelumab) as monotherapy is indicated as maintenance treatment. Regarding patients experiencing progression after platinum salt-based chemotherapy, immunotherapy treatments (pembrolizumab, atezolizumab and nivolumab) have been granted a marketing authorisation in Europe. The French CCAFU 2020-2022 guidelines recommend using pembrolizumab (KEYTRUDA), the only immunotherapy treatment covered in France.

According to ESMO, after relapse from platinum salt-based chemotherapy treatment and immunotherapy treatment (anti-PD1 or anti-PD-L1), the available alternatives are enfortumab vedotin, taxane-based chemotherapy regimens (docetaxel, paclitaxel), vinflunine.

Role of the medicinal product

PADCEV (enfortumab vedotin), as monotherapy is a third-line treatment after a chemotherapy regimen based on platinum salts and an anti-PD-1 or anti-PD-L1 drug in patients with locally advanced or metastatic urothelial carcinoma.

PADCEV (enfortumab vedotin), as monotherapy is a second-line treatment after maintenance treatment with BAVENCIO (avelumab).

The Committee points out that in accordance with the SPC, “patients should be monitored starting with the first cycle and throughout treatment for skin reactions. Patients should be monitored starting with the first cycle and throughout treatment for skin reactions. Appropriate treatment such as topical corticosteroids and antihistamines can be considered for mild to moderate skin reactions. For suspected SJS or TEN, or in case of bullous lesions onset, withhold treatment immediately and refer to specialised care; histologic confirmation, including consideration of multiple biopsies, is critical to early recognition, as diagnosis and intervention can improve prognosis. Permanently discontinue Padcev for confirmed SJS or TEN, Grade 4 or recurrent severe skin reactions. For Grade 2 worsening, Grade 2 with fever or Grade 3 skin reactions, treatment should be withheld until Grade ≤ 1 and referral for specialised care should be considered. Treatment should be resumed at the same dose level or consider dose reduction by one dose level (see Section 4.2 of the SPC).”

Considering the skin toxicity, the Committee recommends setting up oncologist and dermatologist collaboration to define the most suitable treatment (including in particular discontinuing PADCEV (enfortumab vedotin)) from the onset of an initial sign of skin toxicity.

Special recommendations

Considering the uncertainty around the safety of PADCEV (enfortumab vedotin), the Committee shall reassess this proprietary medicinal product within not less than two years from the date of this opinion. The Committee requests to be a recipient of reports analysing the pharmacovigilance data in respect of this proprietary medicinal product. 

Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 11 octobre 2022. L’avis économique porte sur une indication superposable à l’AMM.  

 La CEESP a été en mesure de conclure sur le niveau d’efficience du produit, avec un ratio différentiel coût-résultat (RDCR) de 198 796 €/QALY versus les chimiothérapies à base de taxanes (docétaxel, paclitaxel) et la vinflunine, aux prix revendiqués, sur un horizon temporel de 5 ans.  

PADCEV - Avis économique (pdf)