Novel Resistance Mechanism for Savolitinib in MET-Amplified Gastric Cancer


In a phase II umbrella trial, the VIKTORY trial, 715 gastric cancer patients underwent genomic sequencing and enrolled in the genomic matched cohort. Among the 715 patients, 25 (3.5%) patients harbored MET amplification and received savolitinib, a selective MET inhibitor. Tumor tissue and plasma ctDNA samples from the first three patients were obtained before treatment, during therapy, and at the time of progression. These three patients had a partial response after savolitinib treatment, but the disease progression eventually occurred. After comparing the genomic testing results, MET D1228V/N/H and Y1230C mutations or high-level copy number amplifications of the MET gene might be important resistance mechanisms for savolitinib. More studies should be performed to know the detailed resistance mechanisms of savolitinib in gastric cancer due to limited patient numbers.

JCO Precis Oncol. 2020 Mar 24;4:PO.19.00386.