Preliminary observations of blood-based (BB) molecular testing in a subset of patients with pancreatic cancer (PDA) participating in the Know Your Tumor (KYT) initiative.

Abstract

268 Background: Obtaining an adequate tissue sample for molecular profiling to guide therapy selection for patients with advanced cancers can be clinically difficult, and/or patients may not want to undergo a biopsy. There has been a growing interest in the use of BB tests, including cell free DNA (cfDNA) and exosome/circulating tumor cell based-analyses as surrogates for tumor tissue (TT) testing. Validation of BB tests in PDA is possible because > 90% of PDAs harbor KRAS mutations – thus providing a reliable “internal control.” Methods: The Pancreatic Cancer Action Network (PanCAN) and Perthera initiated an IRB-approved registry trial for patients with pancreatic cancer wherein we facilitated commercially available, CLIA certified multi-Omic profiling including next generation DNA sequencing (NGS), immunohistochemistry, and phosphoproteomics on patient tumor samples. In a subset of these patients, we incorporated BB testing. Results: A KRAS mutation has been identified in 87% of KYT patients based on TT NGS in general. As of this report, 17 BB test results (cfDNA NGS) were available. In 8 patients we were able to compare the cfDNA NGS directly with TT NGS. BB testing identified a KRAS mutation in 1/8 compared to 8/8 from the tumor tissue. Of the 9/17 patients who did not have corresponding TT NGS, a KRAS mutation was found on BB testing in 3/9 samples. 4/17 BB cases overall revealed KRAS mutations, but when cases were filtered for patients with extensive metastatic disease and progressive disease at the time of blood sampling, the KRAS mutation rate increased to 2/5 overall. Actionable findings (i.e. linked to a specific therapeutic option) were identified in 6/17 cases, of which 3/17 had both an actionable mutation and a KRAS mutation. Conclusions: Although we are aware of the limitations of this study, we recommend that for patients who have biopsiable disease, a TT test should still be the gold standard for molecular profiling. For those without biopsiable disease, the KYT program presents an opportunity to determine the parameters that influence the probability of obtaining reliable molecular profiling information from a BB sample.