KEYTRUDA (pembrolizumab) - Mélanome de stade IIB, IIC ou III

Key points

Approval of reimbursement of KEYTRUDA (pembrolizumab):

• as monotherapy for the adjuvant treatment of adult patients and adolescents aged 12 years and older with Stage IIB, IIC or III melanoma and who have undergone complete resection.
• as monotherapy for the treatment of […] adolescents aged 12 years and older with advanced (unresectable or metastatic) melanoma.

Therapeutic improvement?

Therapeutic improvement in the care pathway in all assessed indications.

Role in therapeutic strategy?

The objective of the therapeutic management of localised-stage melanoma is curative. The first line is based on tumour excision surgery.

The lateral excision margins for primary skin melanoma must be adapted to the depth of melanoma invasion according to the following schedule: safety margins of 0.5 cm for cases of in-situ melanoma, 1 cm for tumour thicknesses >0.1 mm and ≤ 1 mm, 1 to 2 cm for tumour thicknesses > 1.1 mm and ≤ 2 mm, and 2 cm for tumour thicknesses > 2 cm.

The sentinel node procedure is an option in cases of localised melanoma. It helps stage melanomas and provides an independent prognostic marker. However, as there is no evidence of a benefit of this procedure in respect of overall survival, it cannot be considered as a curative therapeutic standard.

Considering the latest developments in adjuvant therapy, alpha interferon may no longer be proposed routinely as an adjuvant treatment given the uncertainties around its benefit linked with the lack of clear indication of the specific dose or treatment duration and with high toxicity.

Its use may be limited for specific cases such as Stage IIC ulcerated primary melanoma and when new authorised medicinal products are not accessible.

Adjuvant locoregional radiotherapy may be considered for some specific cases.

The latest updated version of the NCCN guidelines (2022) in the United States incorporating the findings of the KEYNOTE-716 trial, proposes KEYTRUDA as an adjuvant treatment for patients with Stage IIB and IIC melanoma who have undergone complete resection.

At the metastatic stage, immunotherapy is the conventional first-line treatment.

Paediatric-specific guidelines.

Given the rare nature of paediatric melanoma and the complexity of its treatment, there is currently no standard of care. The treatment of paediatric patients generally follows the same principles as for adult patients. According to the European EXPeRT group guidelines published in 2021, the treatment of paediatric patients must be reviewed by a multidisciplinary team including both paediatric oncologists and adulthood melanoma specialists.

Role of KEYTRUDA in the therapeutic strategy:

KEYTRUDA (pembrolizumab) is an adjuvant treatment of Stage IIB and IIC melanoma with a high risk of recurrence for the adult population and for adolescents from 12 years of age.

KEYTRUDA (pembrolizumab) is an adjuvant treatment of completely resected Stage III melanoma and also the first-line treatment of advanced melanoma (unresectable or metastatic), in paediatrics (adolescents from 12 years) in the same way for the adult population.

Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 13/12/2022. 

L’avis économique porte sur une indication plus restreinte que celle demandée au remboursement, à savoir en monothérapie, dans le traitement adjuvant des patients adultes et adolescents âgés de 12 ans et plus atteints d’un mélanome de stade IIB, IIC ayant eu une résection complète. 

Sous les hypothèses retenues par l’industriel, le produit est associé à un RDCR de 33 110 €/QALY gagné versus la surveillance active sur 30 ans. 

L’impact budgétaire associé à l’introduction du pembrolizumab représente une augmentation des dépenses de l’assurance maladie dans l’indication de 41%. 

KEYTRUDA - Avis économique (pdf)