1196P - Identification of targetable alterations using NGS-based liquid biopsy in NSCLC patients

Background

Liquid biopsies are becoming an important tool in Non-Small Cell Lung Cancer (NSCLC) clinical practice, since they are non-invasive, easy to obtain, and allow monitoring alterations along treatments. This work aims to evaluate the usefulness of liquid biopsies to detect targetable alterations by Next Generation Sequencing (NGS).

Methods

58 advanced NSCLC patients (pts) were included in the study. Total circulating free nucleic acids (cfNA) were isolated from 50 blood, 6 pleural fluid, 1 cerebrospinal fluid and 1 ascitic fluid samples. NGS was performed using Oncomine Pan-Cancer Cell-Free Assay and Ion GeneStudio S5 Series. Variant calling was conducted with Ion Reporter Software and its significance was assessed using public databases. Statistical analyses were performed using SPSS software.

Results

cfNA isolation yielded successfully in 86.3% of the cases (cfDNA average was 65.85ng [12.29-1108.50]). 49 pts had sufficient cfNA concentration to be sequenced and passed all the quality controls. From those, 49.0% pts were newly diagnosed and 20.4% were EGFR mutated pts sequenced to identify resistance mechanisms upon progression to 3^rd generation TKIs or 1-2^nd generation in case no T790M mutation was detected by dPCR. 78.8% of the newly diagnosed pts had at least one alteration; which was level 1 of actionability in 12.5% of the cases, and level 1-4 in 52.5%, according to oncoKB database. The most mutated gene was TP53, followed by KRAS (mainly p.G12C and p.G12V). Targetable alterations such as EGFR p.L858R, BRAF p.V600E and a fusion in RET gene were found. Furthermore, survival analyses showed that those pts with at least one alteration had improved prognosis (OS, HR=0.252, p-value=0.033). Regarding EGFR-TKI resistant pts, 80% presented the EGFR sensitizing mutation. Furthermore, mutations in genes such as TP53, KRAS, BRAF and HER2, as well as amplifications in EGFR, MET, ERBB2, MYC and CDK4 genes were found as resistance mechanisms.

Conclusions

These findings support the value of using liquid biopsies to conduct NGS studies that allow a personalized diagnosis and enhance implementation of targeted therapies for lung cancer patients. This study was supported by CB16/12/00350 and P118/00226 from ISCIII, AMACMA and AECC Valencia Scientific Foundation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

FIHGUV - Fundación Investigación Hospital General Universitario de Valencia.

Funding

This study was supported by CB16/12/00350 and P118/00226 from ISCIII and Asociación de Mujeres de Apoyo al Cáncer de Mama (AMACMA). AM is recipient of PhD scholarship from Asociación Española Contra el Cáncer (AECC) Valencia Scientific Foundation.

Disclosure

All authors have declared no conflicts of interest.