Disease monitoring and TKI resistance mutations of EGFR mutation-positive NSCLC patients via circulating tumor DNA.

e21627 Background: 15–40% of NSCLC adenocarcinoma patients harbor EGFR sensitizing mutations. Tyrosine kinase inhibitors (TKI) provide significant clinical benefit in this population, yet all patients will develop resistance. Liquid biopsy has been demonstrated to reliably identify tumor associated somatic EGFR mutations. Quantitative assessment of mutated EGFR driven tumors could potentially be used to monitor disease progression, to assess therapeutic response, and to identify resistance mechanisms. Methods: 106 longitudinal plasma samples from 16 NSCLC patients who were treated with osimertinib as either first line or second line therapy were collected. A series of plasma samples collected during treatment and at the time of disease progression were analyzed with the AVENIO ctDNA Surveillance kit*. Mutations at each time point were identified and reported by the AVENIO software v2.0*. The mutation profile of each patient at different timepoints along with the treatment journey was examined in combination with clinical outcome data. Results: EGFR sensitizing mutations were detected in all plasma samples by sequencing except in 3 cases. Patients responsive to anti-EGFR therapy showed a rapid decrease of EGFR driver mutations to non-detectable levels. Meanwhile, patients who had stable disease or rapid disease progression had stable or slightly decreasing ctDNA levels after receiving the treatment. One patient had a MET amplification, FBXL7 SNV, and EGFR T790M detected at the time of disease progression which were not detected at baseline. One patient had both EGFR L858R and T790M mutations. This patient progressed very quickly on erlotinib. Detection of the T790M mutation decreased upon osimertinib administration, however, the L858R mutation level stayed the same. TP53 mutations were elevated in 3 patients at the time of progression, and could potentially be related to anti-EGFR resistance. Conclusions: This study clearly demonstrated that liquid biopsy could identify resistance mutations beyond EGFR prior to clinical progression. Plasma samples collected prior to or at disease progression could facilitate identification of novel resistant mutations to TKI therapy. Further studies to demonstrate the clinical utility of serial blood EGFR testing in NSCLC management are necessary. *For Research Use Only. Not for use in diagnostic procedures.