Refining Immunotherapy for the Treatment of Gastric Cancer With High Microsatellite Instability
Menée à partir des données portant sur 174, 514 et 682 patients atteints d'un cancer de l'estomac ou d'un cancer de la jonction oesogastrique de stade avancé présentant une haute instabilité des microsatellites et inclus dans 3 essais cliniques de phase II et III, cette étude évalue l'efficacité, du point de vue du taux de réponse, de la survie sans progression et de la survie globale, et la toxicité du pembrolizumab, seul ou en combinaison avec une chimiothérapie
Microsatellite instability (MSI) is characterized by high mutation rates and the generation of frameshift-peptide neoantigens, which foster a highly immunogenic environment with increased peritumoral and tumor-infiltrating lymphocytes. Based on data from cohorts in multiple multicenter single-arm clinical trials in which robust and durable objective responses were observed, pembrolizumab therapy received US Food and Drug Administration approval as the first tumor agnostic of its kind for the treatment of advanced previously treated high-MSI or mismatch repair–deficient tumors in 2017. The rates of high MSI in gastric or gastroesophageal junction cancers are 5% to 20%, posing a challenge to conducting dedicated randomized clinical trials for this small subpopulation. Therefore, data regarding outcomes of patients with high-MSI tumors included in larger studies of gastric or gastroesophageal junction cancer evaluating checkpoint inhibition are welcomed.
JAMA Oncology , 2021