P14 Detection of EGFR/T790M Mutation in Advanced NSCLC Post TKI Treatment: First Experience of Liquid Biopsy in Argentina

Abstract

Genetic alterations in the tyrosine kinase domain of EGFR are key oncogenic events in non–small cell lung adenocarcinoma (NSCLC). In Argentina, 15% of NSCLC patients presents EGFR mutations which direct therapy with EGFR tyrosine kinase inhibitors (TKI) at the moment of diagnosis. Nearly 50% of patients progressing to TKI have T790M resistance mutations of EGFR exon 20. This mutation is detected either in formalin fixed paraffin-embedded (FFPE) tumor tissue and cell free tumor DNA (ctDNA) in plasma (liquid biopsy). This work describes the findings in T790M evaluation in TKI progressed patients either in FFPE tumor tissue or cell free tumor DNA (ctDNA) in the first experience of liquid biopsy application for targeted therapy in Argentina. NSCLC samples in either FFPE tumor tissue or ctDNA were processed from March 2017 to March 2018, from EGFR mutated patients who have radiological evidence of progression to TKI treatment. Samples were evaluated for T790M resistance mutation as requested by Oncologists or Pathologists all over the country. Due to clinical sensitivity and in case of negative results, physicians could request a retest in a newly fresh FFPE or ctDNA sample. T790M mutation was evaluated by digital droplet PCR (ddPCR) methodology (BIORAD QX 200 ™) in the ctDNA samples and by Real Time PCR (EntroGenRT52) for FFPE tumor tissue samples. NSCLC samples in either FFPE tumor tissue or ctDNA were processed from March 2017 to March 2018, from EGFR mutated patients who have radiological evidence of progression to TKI treatment. Samples were evaluated for T790M resistance mutation as requested by Oncologists or Pathologists all over the country. Due to clinical sensitivity and in case of negative results, physicians could request a retest in a newly fresh FFPE or ctDNA sample. T790M mutation was evaluated by digital droplet PCR (ddPCR) methodology (BIORAD QX 200 ™) in the ctDNA samples and by Real Time PCR (EntroGenRT52) for FFPE tumor tissue samples. In TKI progressed EGFRm+ advanced NSCLC patients, T790M resistance mutation in EGFR was found in 42% by ctDNA from plasma and 19% by FFPE tumor tissue. In the retesting scheme, the enriched population was positive in 30% when retesting was by FFPE tumor tissue and in 43% by ctDNA showing the importance of retesting algorithm for the correct identification of patients. The detection of T790M is of radical importance with the advent of new targeted therapies towards this oncogenic driver.