Mechanisms of Acquired Resistance to Savolitinib, a Selective MET Inhibitor in <i>MET</i>-Amplified Gastric Cancer.
case_series · Level IV
Where this comes from
- Record sourced from PubMed, PMID 32923890.
- Also identified by DOI 10.1200/PO.19.00386 and PMC identifier 7446425.
- Licence recorded as CC BY-NC-ND.
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Abstract
Some gastric cancers harbor <i>MET</i> gene amplifications that can be targeted by selective MET inhibitors to achieve tumor responses, but resistance eventually develops. Savolitinib, a selective MET inhibitor, is beneficial for treating patients with MET-driven gastric cancer. Understanding the resistance mechanisms is important for optimizing postfailure treatment options. Here, we identified the mechanisms of acquired resistance to savolitinib in 3 patients with gastric cancer and <i>MET</i>-amplified tumors who showed a clinical response and then cancer progression. Longitudinal circulating tumor DNA (ctDNA) is useful for monitoring resistance during treatment and progression when rebiopsy cannot be performed. Using a next-generation sequencing 100-gene panel, we identified the target mechanisms of resistance <i>MET</i> D1228V/N/H and Y1230C mutations or high copy number <i>MET</i> gene amplifications that emerge when resistance to savolitinib develops in patients with <i>MET</i>-amplified gastric cancer. We demonstrated the utility of ctDNA in gastric cancer and confirmed this approach using baseline tumor tissue or rebiopsy.