EGFR Genotyping of Matched Urine, Plasma, and Tumor Tissue in Patients With Non-Small-Cell Lung Cancer Treated With Rociletinib, an EGFR Tyrosine Kinase Inhibitor. JCO precision oncology Goldman, J. W., Karlovich, C., Sequist, L. V., Melnikova, V., Franovic, A., Gadgeel, S. M., Reckamp, K. L., Camidge, D. R., Pérol, M., Ou, S. I., Liu, S. V., Yu, H. A., Soria, J. C., Socinski, M. A., Mekhail, T. M., Solomon, B. J., Natale, R. B., Otterson, G. A., Papadimitrakopoulou, V., Langer, C. J., Neal, J. W., Despain, D., Yurasov, S., Litten, J. B., Erlander, M., Raponi, M., Wakelee, H. A. 2018; 2: 1-13


Liquid biopsies represent an attractive alternative to tissue biopsies, particularly rebiopsies, in determining patient eligibility for targeted therapies. Clinical utility of urine genotyping, however, has not been explored extensively. We evaluated epidermal growth factor receptor (EGFR) T790M detection in matched urine, plasma, and tissue and the clinical outcomes of patients with advanced non-small-cell lung cancer treated with rociletinib.Tissue (n = 540), plasma (n = 482), and urine (n = 213) were collected from evaluable patients enrolled in TIGER-X, a phase I/II study. Genotyping was performed by therascreen EGFR testing in tissue, BEAMing in plasma, and a quantitative short footprint assay (Trovera) in urine, which was used to further examine discordant samples.Positive percent agreement with tissue T790M results was similar for urine (82%; 142 of 173) and plasma (81%; 313 of 387) genotyping. Urine and plasma together identified more patients who were T790M positive (92%) than tissue alone (83%) among matched samples (n = 177). The ability to identify mutations in plasma was strongly associated with M stage (P < .001); rate of T790M detection for patients with M1a/M0 disease increased from 54% for plasma alone to 85% when urine and plasma were both examined. Objective response rates of patients who were T790M positive were comparable between tumor (34%), plasma (32%), and urine (37%).Clinical response to rociletinib was comparable irrespective of whether T790M status was identified by liquid or tissue biopsy. Combined, urine and plasma identified a higher percentage of patients who were T790M positive than tumor genotyping alone and improved detection of T790M, particularly in the absence of distant metastases. These findings support the noninvasive analysis of urine and plasma before tumor rebiopsy when assessing T790M status.

View details for DOI 10.1200/PO.17.00116

View details for PubMedID 35135111