FIGURE 2 from Functional Heterogeneity in MET Pathway Activation in PDX Models of Osimertinib-resistant EGFR-driven Lung Cancer

Efficacy and determinants of response to osimertinib and savolitinib combination among osimertinib-resistant EGFR-mutant NSCLC PDX models with spatially and temporally heterogenous MET pathway activation. Tumor growth inhibition studies in MET polysomy (A) and MET amplified (B) PDXs. Dashed vertical lines delineate when treatment was stopped. Asterisks signify statistical significance between osimertinib and savolitinib combination and osimertinib alone treatment arms. P values were calculated by t test. P values < 0.05 were considered significant. C, Association between response to osimertinib and savolitinib combination and IHC features (phospho-MET, c-MET), copy number and FISH parameters (number of MET copies and MET/CEP7 ratio). Response is defined as >25 days until reaching tumor size endpoint in osimertinib and savolitinib combination compared with osimertinib treatment alone. Individual circles represent a unique tumor for each represented PDX model. D, Representative c-MET and phospho-MET IHC images of PDX tumors with and without response to osimertinib and savolitinib combination. Scale bars, 50 µm.