Noninvasive comprehensive genomic profiling from plasma ctDNA in pancreatic cancer patients.

Abstract

753 Background: The use of comprehensive genomic profiling (CGP) is increasing in pancreatic ductal adenocarcinoma (PDAC) as knowledge improves regarding molecular drivers of tumorigenesis and effective targeted therapies emerge. However, adequate tissue sampling is often limited. Plasma-based CGP offers a non-invasive approach to assess biomarkers that may impact treatment decisions. Methods: We retrospectively evaluated genomic and clinical data from 97 PDAC patients with circulating tumor DNA (ctDNA) testing from 9/2016-8/2019 (Guardant Health, Inc.). ctDNA analysis included single nucleotide variants (SNV), fusions, indels and copy number variations (CNV) of up to 74 genes. ctDNA results were assessed across clinical variables. We evaluated for actionable alterations. Results: A total of 114 samples were obtained from 97 patients for ctDNA testing. ctDNA alterations were detected in 82% (93/114) of all samples, including 90% (18/20) at diagnosis, 88% (59/67) at progression, and 56% (10/18) while on stable therapy. ctDNA alterations were found at each stage of PDAC: in 25% (1/4) of samples with resectable disease, 75% (3/4) with borderline resectable disease, 82% (9/11) with locally advanced disease, and 85% (81/95) with metastatic disease. One or more KRAS alterations were detected in 55% (51/93) of patients with alterations present. The median maximum mutant allele frequency was similar between the cohort of patients with KRAS detected (0.55%) versus not detected (0.70%). 8% (8/97) of patients had potentially actionable alterations (2 activating BRAF SNVs, 1 ERBB2 CNV, 1 ERBB2 activating SNV, 1 KRAS G12C, and 3 indels in Homologous Recombination Deficiency genes). Median turnaround time was 8 days. 51% (49/97) of patients had both plasma-based CGP and tissue-based CGP. Of these patients, tissue-based CGP showed ≥ 1 alterations detected in 82% (40/49), test failure in 14% (7/49), and no alterations detected in 4% (2/49). Conclusions: Plasma-based CGP detected ctDNA alterations in 90% of samples tested at diagnosis and 82% of all samples. Potentially actionable mutations were found in 8% of patients, with prompt processing time allowing for rapid decision making.