P1.01-52 Cell-Free Tumor DNA (ctDNA) Utility in Detection of Original Sensitizing and Resistant EGFR Mutations in Non-Small Cell Lung Cancer (NSCLC)

Abstract

With the use of personalized therapy the need for repeat biopsies in lung cancer patients (pts) has increased. For most lung cancer pts, a tissue biopsy can be quite challenging and potentially risky.The aim of this study was to evaluate the utility of ctDNA to detect the EGFR original mutation (OM) and to identify the T790M resistance mutation in advanced NSCLC pts who received EGFR-TKI. This is a prospective cohort study utilizing theCobas EGFR ctDNA testing kit V2 in pts with confirmed EGFR-mutant advanced NSCLC by tissue biopsy. The blood was obtained from 66 pts at 4 time points: baseline, time of 1st CT, time of progression, and 1 month after starting new treatment. From January 2017 to January 2019, 66 pts were enrolled in the study, of which 41(62%) had an exon 19 deletion and 25(38%) had an exon 21 mutation. 23/66 pts were TKI naive and 43/66 were already on TKI treatment. Adequate ctDNA was found in the plasma of 97% of cases. The OM was identified in 42 % of pts at first blood test with higher detection rates in TKI naïve pts 12/23(52%) compared to 16/43(37%) in TKI group. Best response to first line TKI was evaluated in 64 pts; in 56 (88%) pts, disease was controlled (CR+PR+SD) with TKI, in 8 (12%) pts the treatment had failed and was discontinued. A significant correlation between OM detection and response to first line TKI was found (p =0.05) with higher detection rate in non-responders 6/8(75%) compared to responders 21/56 (38%). In TKI naïve pts OM was detected in 4/5(80%) of non-responders and in TKI group in 2/3 (67%) pts. The resistance mutation (T790M) was detected in 12/66 (18%) pts. All 12 (100%) pts initially responded to TKI and OM was no longer detected. Median duration of TKI until progression was 25.5 (SD 12.7) mo. The OM re-occurred in 11/12 (92%) at the time of progression. ctDNA can be noninvasively assessed in the circulation and be used to monitor responses to treatment and detect development of secondary resistance. The re-occurrence of OM on repeat liquid biopsy seems to be a sign of resistance to first line treatment. In the future, instead of extensive imaging and invasive tissue biopsies, ctDNA test by NGS panel could be used to find other mutations and to guide cancer treatment decisions.