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KEYTRUDA 25 mg/ml (pembrolizumab)
Reason for request
Key points
Favourable opinion for reimbursement of KEYTRUDA (pembrolizumab) in combination with platinum and fluoropyrimidine-based chemotherapy in the first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma of Siewert type 1 only, in adults whose tumours express PD-L1 with a CPS ≥ 10.
Unfavourable opinion for reimbursement in the first-line treatment of locally advanced unresectable or metastatic HER-2 negative Siewert type 2 or 3 gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 10.
What therapeutic improvement?
Therapeutic improvement compared to platinum and fluoropyrimidine-based chemotherapy in the first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma of Siewert type 1 only, in adults whose tumours express PD-L1 with a CPS ≥ 10.
Role in the care pathway?
The curative treatment for oesophageal cancers is surgery preceded by radiochemotherapy combining carboplatin and paclitaxel. In the event of locally advanced tumours or a health status unfavourable to surgery, curative treatment may also consist of radiochemotherapy alone, potentially supplemented by salvage surgery in the event of an incomplete response.
In patients with locally advanced unresectable (in the event of contraindication to radiotherapy) or metastatic oesophageal squamous cell carcinoma or adenocarcinoma, use of systemic treatment alone (palliative chemotherapy) is the standard treatment. The main chemotherapy products used in combination are cisplatin and 5- fluorouracil. Other regimens, such as the FOLFOX regimen combining fluorouracil-oxaliplatin-folinic acid, are sometimes used as a treatment option.
Currently, advanced unresectable or metastatic Siewert type I GEJC adenocarcinomas are treated in the same way as oesophageal cancers. In certain metastatic gastro-oesophageal junction (GEJC) adenocarcinomas over-expressing HER 2 (15-20% of cases), treatment with a targeted therapy (trastuzumab) may also be proposed in combination with chemotherapy.
At this stage of the disease (unresectable, advanced or metastatic), the median overall survival is less than one year with fluoropyrimidine-based chemotherapies.
Role of the medicinal product in the care pathway
KEYTRUDA (pembrolizumab) in combination with platinum and fluoropyrimidine-based chemotherapy is a first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma of Siewert type 1 only, in adults whose tumours express PD-L1 with a CPS ≥ 10.
In the absence of data given the inclusion criteria of the KEYNOTE-590 study, KEYTRUDA (pembrolizumab) in combination with platinum and fluoropyrimidine-based chemotherapy has no role in the care pathway for patients with Siewert type 2 or 3 gastroesophageal junction adenocarcinoma.
Clinical Benefit
| Substantial |
The Committee deems that the clinical benefit of KEYTRUDA (pembrolizumab), in combination with platinum and fluoropyrimidine-based chemotherapy, is substantial in the first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma of Siewert type 1 only, in adults whose tumours express PD-L1 with a CPS ≥ 10. |
| Insufficient |
The Committee deems that the clinical benefit of KEYTRUDA (pembrolizumab), in combination with platinum and fluoropyrimidine-based chemotherapy, is insufficient to justify public funding cover in the first-line treatment of locally advanced unresectable or metastatic HER-2 negative Siewert type 2 or 3 gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 10.
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Clinical Added Value
| moderate |
The Transparency Committee considers that KEYTRUDA (pembrolizumab) in combination with platinum and fluoropyrimidine-based chemotherapy provides a moderate clinical added value (CAV III) compared to chemotherapy alone in the first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative Siewert type 1 gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 10.
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Avis économique
Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 1er février 2022.
L’évaluation porte sur une indication plus restreinte que l’AMM à savoir pembrolizumab en association à une chimiothérapie à base de sels de platine et de fluoropyrimidine dans le traitement de 1re ligne du cancer de l’œsophage ou d’un adénocarcinome de la JGO HER-2 négatif uniquement de type I (classification Siewert), localement avancés non résécables ou métastatiques, chez les patients adultes dont les tumeurs expriment PD-L1 avec un CPS ≥ 10.
La CEESP a été en mesure de conclure sur le niveau d’efficience du produit, avec un RDCR de 107 407 €/QALY versus un « Bras comparateur mixte », au prix de vente en vigueur et sur un horizon temporel de 10 ans.
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 290% dans cette indication, pour une population cible de 5 625 patients cumulés sur 3 ans.
> KEYTRUDA - Avis économique (pdf)
