KEYTRUDA (pembrolizumab) - Cancer colorectal métastatique

Key points

Favourable opinion of KEYTRUDA (pembrolizumab) for reimbursement as monotherapy for the first-line treatment of metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer in adults, only in patients unresectable from the outset.

Unfavourable opinion for reimbursement in patients initially resectable.

What therapeutic improvement?

Therapeutic improvement compared to chemotherapy ± targeted therapy.

Role in the care pathway?

In patients initially resectable, curative metastatic surgery is recommended, accompanied by perioperative chemotherapy (pre and postoperative). In patients initially unresectable, the use of targeted therapies, in combination with chemotherapy, is recommended as first-line treatment (except in the event of contraindications: organ failure, poor ECOG score, heart failure).

The recommended chemotherapy protocols (ESMO) are:

1) in combination with bevacizumab:

• double chemotherapies: FOLFOX/CAPOX/FOLFIRI

      FOLFOXIRI6 triple chemotherapy, in selected patients (considered to be “fit” and for whom cytoreduction is targeted)

• single-agent chemotherapy with 5-FU, in patients unable to tolerate a more aggressive treatment

2) in combination with panitumumab or cetuximab: FOLFOX/FOLFIRI chemotherapies double.

Some tumours may be microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). However, apart from KEYTRUDA (pembrolizumab), there is currently no specific treatment for these patients. Their management remains identical to that for patients without MSI-H/dMMR disease.

Role of the medicinal product in the care pathway

KEYTRUDA (pembrolizumab) is a first-line treatment of metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer in adults initially unresectable.

Given the initially increased risk of progression (first 2-3 months) in patients having received pembrolizumab, compared to those having received chemotherapy ± targeted therapy, the Committee recommends caution when treating patients at a high risk of progression/early death. The Committee considers that the therapeutic decision should be taken after a documented proposal resulting from a multidisciplinary team meeting.

For second-line treatment (outside the scope of the current indication for KEYTRUDA (pembrolizumab)) in BRAF V600E mutation-positive patients, the Committee highlights that the encorafenib-cetuximab combination has only been assessed in patients having received a first line of chemotherapy +/- targeted therapy. The role of the encorafenib-cetuximab combination, as second-line therapy, in patients having received a first line of treatment with KEYTRUDA (pembrolizumab) is not currently known. In the absence of available data enabling assessment of the best strategy in BRAF V600E mutation-positive patients, the Committee recommends that this strategy be discussed during a multidisciplinary team meeting.

Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 26 octobre 2021. 

La CEESP a été en mesure de conclure sur le niveau d’efficience du produit, avec un ratio différentiel coût-résultat (RDCR) de 47 333 €/QALY versus les traitements standards, au prix de vente en vigueur.  

Au prix public du pembrolizumab, et selon les parts de marchés prévisionnelles envisagées par l’industriel, la mise à disposition du pembrolizumab dans la nouvelle indication revendiquée représente une augmentation des dépenses de l’assurance maladie de 110% dans cette indication, pour une population cible de 4 062 patients cumulés sur 3 ans. 

> KEYTRUDA - Avis économique (pdf)