TUKYSA (tucatinib)

Key points

Favourable opinion for reimbursement in combination with trastuzumab and capecitabine, for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least 2 prior anti-HER2 treatment regimens.

What therapeutic improvement?

Therapeutic improvement compared to the trastuzumab plus capecitabine combination used alone.

Role in the care pathway?

According to European (ESMO 2020) and French guidelines, the first-line treatment of metastatic HER2-positive breast cancer is based on the combination of two anti-HER2 agents: trastuzumab and pertuzumab combined with taxane-based chemotherapy (docetaxel or paclitaxel). As second-line therapy, KADCYLA (trastuzumab emtansine) is currently the option favoured by all the guidelines. Other options such as lapatinib/capecitabine and trastuzumab/lapatinib combinations are also considered to be alternatives at this stage of the disease. Chemotherapy, particularly with capecitabine (XELODA and generics), is also recommended in combination with trastuzumab (HERCEPTIN and biosimilars) based on validated guidelines (ESMO, St Paul de Vence, regional standards, etc.) in the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens.

Role of the medicinal product in the care pathway

Considering demonstration of the superiority in terms of overall survival of the addition of TUKYSA (tucatinib) to trastuzumab and capecitabine compared to the trastuzumab plus capecitabine combination used alone, the combination of TUKYSA (tucatinib) with trastuzumab and capecitabine is the treatment option to be favoured over the trastuzumab plus capecitabine combination as third-line treatment in adult patients following the failure of trastuzumab/pertuzumab combined with a taxane then trastuzumab emtansine. The Committee highlights the fact that these results were obtained in a population including patients with brain metastases (around half of the patients in the study).

The choice of third-line treatment in adult patients with HER2-positive locally advanced or metastatic breast cancer should consider, in particular, the level of evidence of the demonstration in terms of efficacy as well as the safety profile of the treatments available. In particular, as regards TUKYSA (tucatinib) in combination with trastuzumab and capecitabine, this choice should take into account demonstration of an increase in overall survival compared to the trastuzumab plus capecitabine combination used alone, as well as its specific safety profile, marked by very frequent gastrointestinal disorders (diarrhoea) and hand-foot syndromes.

Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 20 juillet 2021.

L’avis économique porte sur une indication superposable à celle demandée au remboursement, à savoir en association au trastuzumab et à la capécitabine pour le traitement des patients adultes atteints d’un cancer du sein HER2 positif localement avancé ou métastatique ayant reçu précédemment au moins 2 traitements anti-HER2.

La CEESP a été en mesure de conclure sur le niveau d’efficience du produit, avec un ratio différentiel coût-résultat (RDCR) de 298 148 €/QALY versus trastuzumab emtasine (Kadcyla), au prix revendiqué. Ce niveau de RDCR élevé est probablement sous-estimé puisqu’il ne prend pas en compte l’utilisation des traitements selon la posologie décrite dans les résumés des caractéristiques des produits.

Aucune analyse d’impact budgétaire n’a été déposée.

> TUKYSA - Avis économique (pdf)