Circulating tumor DNA (ctDNA) based liquid biopsies (LB) have significantly advanced clinical care for NSCLC patients by improving access to molecular testing. A key benefit of certain LB approaches is fast turnaround time (TAT), which can accelerate treatment initiation. We prospectively evaluated the feasibility, accuracy, and TAT of OncoBEAM EGFR, KRAS and BRAF genotyping in a cohort of NSCLC patients seen at a single institution in routine clinical practice. Alterations in these genes directly inform the use of approved (EGFR, BRAF) and emerging (KRAS G12C) targeted therapies, and due to mutual exclusivity with gene fusions in ALK/ROS/RET, may obviate the need for additional molecular testing.
Whole blood samples (n = 187) were collected from metastatic NSCLC patients and sent to a CLIA lab for OncoBEAM digital PCR analysis of EGFR (exon 19 del, L858R, T790M, C797S), KRAS (codons 12, 13, 61), and BRAF V600E. Forty samples were analyzed prospectively to assess TAT and 147 samples were analyzed retrospectively. Samples with sufficient residual plasma (n = 176) were tested with SafeSEQ, an orthogonal NGS-based LB assay. TAT was calculated as number of days from specimen receipt to results.
The mean TAT of OncoBEAM results for 40 samples prospectively tested was 4.25 ± 0.98 days (95% CI: 3.94–4.56), with the most and least rapid results delivered within 3 and 6 days, respectively. For the same 40 patients, the mean TAT of tissue-based genotyping was 12.13 ± 4.42 days (95% CI: 10.68–13.59). Of 54 (29%) ctDNA positive patients in the full cohort (n = 187), EGFR, KRAS, and BRAF mutations were detected in 30 (56%), 25 (46%), and 0 samples, respectively. The median mutant allele frequency (MAF) for all mutations detected by OncoBEAM was 0.50% (range: 0.04–50.84%), where 64% and 23% of mutations were detected with MAF <1% and <0.1%, respectively. Concordance of results between OncoBEAM and SafeSEQ in 176 replicate samples revealed an overall percent agreement of 99.6% with strong linear correlation of MAF (R2 = 0.98).
OncoBEAM LB enables sensitive and accurate genotyping results within 5 days, ∼3x faster than the TAT of tissue genotyping results, which carries significant implications for enabling rapid implementation of targeted therapies for NSCLC patients.
Legal entity responsible for the study
H. Sloane: Full/Part-time employment: Sysmex Inostics, Inc. D. Edelstein: Full/Part-time employment: Sysmex Inostics, Inc. F. Jones: Full/Part-time employment: Sysmex Inostics, Inc. J. Preston: Full/Part-time employment: Sysmex Inostics, Inc. F. Holtrup: Full/Part-time employment: Sysmex Inostics, Inc. H. Quinn: Full/Part-time employment: Sysmex Inostics, Inc. All other authors have declared no conflicts of interest.