Dual checkpoint blockade for microsatellite instability-high colorectal cancer
Mené sur 707 patients atteints d'un cancer colorectal non résécable ou métastatique et présentant une instabilité des microsatellites élevée ou une déficience du système de réparation des mésappariements de l'ADN (durée médiane de suivi : 47 mois), cet essai randomisé international de phase III évalue l'intérêt, du point de vue de la survie sans progression, d'ajouter de l'ipilimumab au nivolumab
Metastatic colorectal cancer with microsatellite instability-high or mismatch repair-deficient status represents a distinct tumour subtype that accounts for around 5% of total colorectal cancer cases. Although standard chemotherapy has some efficacy in this subtype, immune checkpoint inhibition has shown promising activity, primarily due to the high tumour mutational burden and increased expression of tumour-specific neoantigens. Despite the progress of immunotherapy in microsatellite instability-high or mismatch repairdeficient colorectal cancer, only around 40% of patients have durable clinical responses with single-agent PD-1 blockade. Indeed, a substantial proportion of patients with microsatellite instability-high or mismatch repairdeficient colorectal cancer have primary or acquired resistance to anti-PD-1 therapy, underscoring a key unmet need for novel immunotherapy strategies and combination approaches in this population.
The Lancet 2024