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Invited Commentary
April 1, 2021

Refining Immunotherapy for the Treatment of Gastric Cancer With High Microsatellite Instability

Author Affiliations
  • 1Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
JAMA Oncol. Published online April 1, 2021. doi:10.1001/jamaoncol.2021.0091

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.1 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 2017.2 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.3 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.

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