PD-1 inhibition in metastatic dMMR/MSI-H colorectal cancer
Mené sur 74 patients atteints d'un cancer colorectal métastatique avec déficience des gènes MMR ou instabilité élevée des microsatellites (durée médiane de suivi : 12 mois), cet essai international de phase II évalue l'efficacité, du point de vue de la réponse objective et du contrôle de la maladie, et les effets secondaires du nivolumab
Restoring the host immune response against cancer cells through blockade of the PD-1 axis is an established treatment strategy for several tumour types. Findings of initial studies of PD-1 inhibitors in metastatic colorectal cancer were not especially promising. Nonetheless, they suggested the existence of a subset of patients who might benefit substantially from immunotherapy. These patients were identified as having DNA mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) tumours, which are characterised by a high mutational load, high numbers of antigenic neo-epitopes, abundant infiltration of CD8+ cytotoxic lymphocytes, and upregulation of immune checkpoints.