Concordance of liquid biopsy and tissue CGP for identification of guideline-recommended actionable variants.

Abstract

e15061 Background: Comprehensive genomic profiling (CGP) is essential for managing patients (pts) with advanced solid tumors. Liquid biopsy (LBx) and tissue CGP are known to provide complementary information; however, concordance may be influenced by factors such as test intervals, tumor shedding and heterogeneity, and differences in genomic regions covered by each assay. We evaluated two assays performed within short intervals to determine concordance, LBx or tissue only detection, and factors impacting detection. Methods: Actionable, NCCN-guideline variants were assessed in 99 advanced cancer pts tested by similar CGP platforms, PanTracer LBx and PanTracer Tissue, within a 90-day interval. Results: Among the 99 pts, 68% had lung, 19% colorectal, and 13% breast cancer; 58% were females. LBx and tissue testing was performed within 30 days in 66 pts (median 9 days; range 0–28) and 32–90 days in the remaining 33 pts (median 47 days). Median result turnaround time (TAT) was 8 days for LBx (range 5–46) and 28 days for tissue (range 10–125). Guideline-recommended actionable alterations (N = 48) were identified in 41 pts (42%) with detection rates of 36% in lung (24/67) and 54% in colorectal (10/19) and breast cancer (7/13). Of these, 54% (26/48) were detected by both assays in 23/41pts (56%). Concordance rate varied by tumor type: 50% for lung (12/24), 60% for colorectal (6/10) and 71.5% for breast cancer (5/7). Three variants (6%) were detected only by LBx; two ESR1 variants in a breast cancer pt (with a third concordant ESR1 variant) and an ALK fusion in a lung cancer pt with no further variants. The remaining 19 variants (40%) were detected only in tissue in 17 pts (41.5%), none of whom had concordant or LBx-only variants. Importantly, median ctDNA-estimated tumor fraction (TF) was higher in pts with concordant (7.85%; range 0.11–67%) and LBx-only variants (9.41%; range 0.31–18.5%) compared to tissue-only variants (0.21%; range 0.07–0.86%). Median LBx-tissue testing interval in pts with concordant or tissue-only variants was 21 days. Conclusions: LBx identified 60% of actionable variants (29/48; concordant and LBx-only) in 24/41 pts (59%) underscoring its clinical value for faster, urgent treatment decisions due to improved TAT. Tissue testing in low-shedding tumors can mitigate LBx false negatives and expand access to targeted therapies. Analyses evaluating LBx detection and other actionable/informative alterations (e.g. resistance mechanisms, clinical trial access) will be presented.