Meeting
2019 ASCO Annual Meeting
Clinical, pathological and genetic predictors of patient-derived xenograft (PDX) engraftment in EGFR-mutated lung adenocarcinoma (LUAD).
Authors
Sebastiao N. Martins-Filho
University Health Network, University of Toronto, Toronto, ON, Canada
Sebastiao N. Martins-Filho , Jessica Weiss , Nhu-An Pham , Michael Cabanero , Aline Fusco Fares , Erin L. Stewart , Devalben Patel , Judy McConnell , Penelope Ann Bradbury , Adrian G. Sacher , Natasha B. Leighl , Alexandria Grindlay , Frances Allison , Ming LI , Kazuhiro Yasufuku , Frances A. Shepherd , Nadeem Moghal , Ming Sound Tsao , Geoffrey Liu
Organizations
University Health Network, University of Toronto, Toronto, ON, Canada, University Hospital Network (UHN) Biostatistics Department, Toronto, ON, Canada, Princess Margaret Cancer Center, Toronto, ON, Canada, Princess Margaret Hospital, Toronto, ON, Canada, Princess Margaret Cancer Centre, Toronto, ON, Canada, Princess Margaret Cancer Centre, University Health Network, Ontario Cancer Institute, Toronto, ON, Canada, University Health Network, Toronto, ON, Canada, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada, University of Toronto, Toronto, ON, Canada, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, ON, Canada, Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Research Funding
Other
Background: PDX are useful preclinical models to study drug response and resistance. Different specimen types have been used to generate PDX models including histological (surgery and CT-guided biopsy) and cytological preparations (EBUS and pleural effusions). We hypothesize that engraftment is not stochastic and is affected by many factors including sample type and tumor pathological and molecular properties. To improve sample selection and cost-effectiveness of PDX experiments, we investigated clinical, histological and genetic correlates of engraftment in EGFR-mutated LUAD. Methods: We assessed PDX engraftment from 96 surgical resections, 13 CT-guided biopsies, 21 EBUS and 14 pleural effusions of EGFR-mutated LUAD. Sixty-five samples, including 6 engrafted (XG) and 54 non-engrafted (noXG) were evaluated by exome sequencing. Results: Engraftment was successful in 9/96 (9%) surgical resections, 6/13 (46%) CT-guided biopsies, and 0/35 cytological samples. Biopsies taken at time of treatment failure (compared to treatment naive biopsies) correlated with greater engraftment (p=0.007, AUC = 0.68). Multivariable regression analysis of clinical variables at the time of sampling identified advanced (vs early) stage (p = 0.003) and histological (vs cytological) preparations (p < 0.001) as the strongest predictors of engraftment (AUC = 0.79). Among tumor histologic features, solid (vs lepidic, acinar and papillary) pattern was associated with greater engraftment (p < 0.001). Presence of EGFR-T790M (p = 0.004) and TP53 (p = 0.009) mutations were associated with greater engraftment; all XG samples carried TP53 mutations. EGFR-Ex19del (p = 0.076) showed a trend towards engraftment whereas EGFR-L858R (p = 0.086) trended towards non-engraftment. Conclusions: Advanced stage, post-therapy tumors, T790M+ and TP53+ EGFR-mutated LUAD samples obtained for histological processing are more likely to engraft as PDXs. Despite low engraftment rates, these models are useful to study novel therapeutic strategy and elucidation of resistance mechanisms.
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Abstract Details
Session Type
Poster Session
Session Title
Developmental Therapeutics and Tumor Biology (Nonimmuno)
Track
Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Sub Track
Other Developmental Therapeutics
Citation
J Clin Oncol 37, 2019 (suppl; abstr 3110)
DOI
10.1200/JCO.2019.37.15_suppl.3110
Abstract #
3110
Poster Bd #
102
Abstract Disclosures
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