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ENHERTU (trastuzumab deruxtecan)

Opinions on drugs - Posted on Jun 24 2021

Reason for request

First assessment

Key points

Favourable opinion for reimbursement as monotherapy 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.

Maintenance of this opinion is conditional on the reevaluation of this medicinal product within a maximum period of 18 months from the date of this opinion based on the results of the phase 3 DESTINY-BREAST 02 study (results on PFS expected for March 2022 at the latest).

What therapeutic improvement?

No clinical added value in the therapeutic strategy on the basis of currently available data.

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/capecitabin and trastuzumab/lapatinib combinations are also considered to be alternatives at this stage of the disease.

Recently, the American NCCN 2021 guidelines included tucatinib (in combination with trastuzumab and capecitabin) as third-line treatment following the failure of tratuzumab/pertuzumab combined with a taxane then trastuzumab emtansine, with a level 1 grade of recommendations (high level of evidence), following the demonstration of its superiority in terms of progression-free survival and overall survival in a phase 2 study versus trastuzumab and capecitabin.

Role of ENHERTU (trastuzumab deruxtecan) in the care pathway:

ENHERTU (trastuzumab deruxtecan) is a third-line treatment option following the failure of trastuzumab/ pertuzumab combined with a taxane then trastuzumab emtansine. In the absence of any comparative data, its role compared to the available alternatives remains to be specified. It should be noted that the phase 2 non-comparative study having assessed the medicinal product only included patients in good general condition, with active brain metastases being of the exclusion criteria.

The Committee reiterates that in this same treatment line, there is an alternative with a better level of evidence, represented by tucatinib [TUKYSA] (MA obtained on 11/02/2021).






Clinical Benefit


The Committee deems that, on the basis of current knowledge, the clinical benefit of ENHERTU (trastuzumab deruxtecan) is moderate in the MA indication.

Clinical Added Value

no clinical added value


  • the not very robust quality of the research evidence for its efficacy in terms of tumour response derived from a non-comparative phase 2 study in a heterogeneous population (ranging from 2 to more than 5 previous treatment lines for the advanced stage),
  • the absence of a quality of life assessment,
  • the safety profile of trastuzumab deruxtecan marked, in particular, by the occurrence of serious adverse events (AEs) in more than a quarter of cases and of ≥ grade 3 AEs in more than two thirds of cases, and
  • the existence of medicinal alternatives at this stage of the disease,

the Committee considers that, on the basis of currently available data, ENHERTU (trastuzumab deruxtecan) provides no clinical added value (CAV V) in the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens.


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 chez les patientes adultes présentant un cancer du sein HER2 positif non résécable ou métastatique ayant reçu préalablement au moins deux lignes de traitement anti-HER2. La CEESP n’a pas été en mesure de conclure sur l’efficience du produit en raison d’une réserve majeure sur l’extrapolation et d’une incertitude globale majeure.

Une analyse d’impact budgétaire a été réalisée en complément de l’évaluation de l’efficience. Les résultats de l’AIB ne peuvent être retenus comme valides en raison d’une réserve majeure.

> ENHERTU - Avis économique (pdf)


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