Dual Immune Checkpoint Blockade in Microsatellite Instability-High Cancers—Effective, but for Whom and When?
Mené sur 52 patients atteints d'un cancer présentant une déficience du système de réparation des mésappariements de l'ADN ou une haute instabilité des microsatellites et de stade avancé (hors côlon-rectum ; âge médian : 62 ans), cet essai non randomisé de phase II évalue l'efficacité, du point de vue du taux de réponse objective et de la survie sans progression à 6 mois, et la toxicité d'un traitement combinant nivolumab et ipilimumab
In their study, Carlino et al1 report their results from a phase 2 basket trial evaluating dual immune checkpoint blockade (ICB) with ipilimumab and nivolumab in patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) noncolorectal cancers. The trial enrolled 52 patients across 17 tumor types, with endometrial cancer comprising half of the cohort. Half of the patients were treatment naive, and half had received 1 prior line of therapy; only 1 had prior exposure to checkpoint inhibition. The overall objective response rate was 63%, including 5 complete responses. An additional 8 patients achieved stable disease, yielding a disease control rate of 79%. Eleven patients experienced progression, either clinically before the first imaging or at first imaging assessment. Responses were similar between treatment-naive and previously treated patients, and 20 of 26 patients with endometrial cancer achieved disease control. Immune-related adverse events were common, occurring in 75% of patients, with 23% experiencing grade 3 or higher toxicity.
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JAMA Oncology , commentaire, 2025