Molecular characterization of patients with advanced lung adenocarcinoma at diagnosis with next generation sequencing by liquid biopsy in the Mexican population.

Abstract

e21511 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Tumor biopsy represents the standard for molecular diagnosis, nevertheless it is not always feasible to obtain. Liquid Biopsy (LB) may offer an alternative in the first line setting. Methods: Retrospective review of case files and next generation sequencing report (NGS) from LB from patients in a Validation Trial, performed from January 2018 to September 2019. We present the molecular alterations and clinical characteristics of the population. Results: 147 records and LB reports of patients 18 years and older with metastatic lung adenocarcinoma without prior treatment were included. 40% of the population had been selected based on a commercial local PCR test for EGFR (Idylla). 49% of them were female with Mean age of 60.9 ± 12.7. 56% had a history of smoking with an average packs/year of 20.5 (1-156) and 39% had exposure to wood smoke, 92% had an ECOG 0-1. 65 % of the Patients were diagnosed in Clinical Stage (8th Edition) IVA and 22% in IVB. 13% had SNC metastasis. The LB detected genomic alterations in 85.5% of the cases. 78% represent pathogenic mutations and 7.5% variants of uncertain significance (VUS).14.5% of the biopsies could not detect any ctDNA. The most frequent aberrations reported were TP53 in 51.7%, KRAS 16%, EGFR 16%, ALK 9%, PIK3CA 4%, RET 4%, BRAF 3%, BRCA 3, and HER2 3%. In addition, 20% had bTMB ≥10. Only 20% of the patients could receive a targeted therapy or immunotherapy of the potential ≈50%. Most cases had co-mutations (1-6 x case). Looking for factors associated with the presence of bTMB by a logistic regression model, it was possible to identify the presence of CNS metastases and smoking as identified with an OR of 3,688 (p = 0. 0.042) and 3.952 (p = 0. 024) respectively. Conclusions: It is feasible to have tumor molecular analysis through liquid biopsy in most cases, with genetic alterations previously reported in tumor tissue in the first line setting. [Table: see text]