EGFR-mutated lung adenocarcinomas from patients who progressed on EGFR-inhibitors show high engraftment rates in xenograft models.

Patient-derived xenografts (PDX) are useful preclinical models to study cancer biology and mechanisms of drug response/resistance, particularly in molecularly targetable tumors. However, PDX engraftment may not be stochastic. We investigated clinical, histological and molecular features associated with PDX engraftment in a large cohort of EGFR-mutated lung adenocarcinoma (LUAD). Samples were collected by different methods from patients at various disease stages and phases of treatment. PDX engraftment was defined as an ability to passage tumors twice in NOD-SCID mice. Uni- and multivariate logistic regression evaluated factors associated with engraftment. Among 138 EGFR-mutated LUAD implanted into NOD-SCID mice, the overall engraftment rate was only 10% (14/138). However, engraftment was significantly higher in specimens from surgical resections or core-needle biopsies collected from metastatic sites (5/5; 100%) or from patients who had progressed on EGFR-inhibitors (7/10; 70%). Engrafted tumors usually showed poor histological differentiation, a solid morphologic pattern, and presence of either EGFR T790 M and/or TP53 mutations. Population level analyses of mutant EGFR-PDX show that these models might not fully recapitulate the inter-patient heterogeneity of EGFR-LUAD. However, mutant EGFR-PDXs may be useful to address key clinical questions, notably development of resistance to EGFR-inhibitors and disease progression to distant metastases.