Impact Of Liquid-Biopsy In The Therapeutic Decision Making Process In A Peruvian Institution.

e18761 Background: Liquid biopsy is a non-invasive method that allows us to understand the molecular changes occurring in the tumor in real time due to heterogeneity and/or therapeutic pressure. In the present work we sought to elucidate the ability of liquid biopsy to re-shape treatment decisions in our institution. Methods: A total of 25 patients (pts) with advanced gastric (AGC; n = 5), colorectal (ACC; n = 5) and non-small cell lung cancers (ALC; n = 15) in second or third line of treatment were analyzed by a commercially available plasma cell-free DNA (cfDNA) next generation sequencing (NGS; Guardant360®). The comprehensive -cfDNA NGS panel evaluates point mutations, amplifications, fusions, and insertion-deletion alterations in up to 73 genes. Type of genomic alterations and concordance with tissue testing were examined. Results: Ninety-two percent of patients (23/25) had ≥1 ctDNA alteration(s). AGC showed the highest somatic alteration burden (17.4%; [1.4%-49%]), followed by ACC (10.84%; [0%-22.3%]) and ALC (2.74%; [0.1%-23%]). The most common alterations detected by plasma cfDNA were TP53 (72%), EGFR (36%) and KRAS (24%). In our cohort, 20% (5/25) of pts changed treatment for a FDA-approved drug available at our institution due to the plasma cfDNA results; among these cases, we had EGFR and ERBB2 mutations not detected in initial biopsy of two ALC pts (744_K745insKIPVAI [Exon 19 Insertion] and L755P, respectively) changing therapeutic indication in both pts (2/15, 13.3%). Two ERBB2 amplifications in AGC pts were detected by ctDNA, but not at initial biopsies (2/5, 40%). KRAS alterations (mutation/ amplification) were present in 3 out of 5 cases of ACC by ctDNA, one KRAS mutant was not detected at initial tissue biopsy, allowing change in therapeutic decision (1/5, 20%). Response rates (RR) in pts with ALC (2) and ACC (1) who started treatment based on Guardant360 results was 100%, reducing time to start of treatment by 50% compared to NGS in FFPE. Conclusions: In our cohort, 20% of pts evaluated by plasma cfDNA have a treatment change, allowing early identification of biomarkers of response / resistance to targeted therapies, corroborated by a significative RR.