James Hamrick, MD, Chairman of the Caris Precision Oncology Alliance, discusses outcomes of immune checkpoint inhibition in patients with Epstein-Barr virus-associated gastric cancer (EBVaGC).
EBVaGC is a malignant tumor caused by BART miRNAs and BARF1 promoting oncogenesis after EBV infection. EBVaGC is characterized by a DNA methylation phenotype, PD-L1 and PD-L2 overexpression, and frequent alterations in the PIK3CA gene. The condition is found in around 9% of gastric cancers.
A recent study looked at outcomes of immune checkpoint inhibition (ICI) in EBVaGC, evaluating the efficacy of next generation sequencing in replacing EBER ISH as standard for detection, and identifying molecular features of ICI-responsive EBVaGC. Retrospective data was collected on 91 patients with metastatic EBVaGC and were stratified into patients receiving ICI alone or with chemotherapy, and by 1L vs. 2L+.
Patients who received first-line chemotherapy plus ICI achieved a 49% objective response rate, median progression-free survival of 8.3 months, and median overall survival of 38 months. This is compared with a median overall survival of 18 months in patients receiving first-line chemotherapy alone. Patients receiving ICI alone achieved a 49% overall objective response rate with 1L and later line mean progression-free survival of 6 months and 3.2 months, respectively, which increased to 10 months and 6.6 months when limiting to PD-L1 CPS greater than or equal to 5.
Univariate analysis for progression-free survival among all patients demonstrated improved outcomes in those where PD-L1 CPS score was greater than or equal to 5. EBV detection by MSK-IMPACT and Caris achieved over 98% positive agreement and 99.9% negative agreement. These results demonstrate the next generation sequencing can be a reliable detector of EBVaGC.
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