Apport de la recherche des mutations de l’EGFR sur prélèvement sanguin à la thérapeutique du cancer bronchique non à petites cellules (CBNPC)

Abstract

The detection of EGFR mutations is an essential prerequisite in the management of advanced non-small cell lung cancer (NSCLC). Identifying activating or resistance mutations enables patients harboring these alterations to benefit from anti-EGFR tyrosine kinase inhibitors (TKIs). Liquid biopsy, as a non-invasive method, helps overcome several limitations of tissue biopsy, particularly when tissue samples are insufficient, of poor quality, or when monitoring disease progression. In this context, our study aimed to identify EGFR mutations using liquid biopsy in patients with advanced NSCLC, in order to guide therapeutic decision-making. Materials and Methods: EGFR mutation analysis was performed by qPCR in 70 patients with stage III or IV NSCLC. Among them, eight patients had experienced disease progression while on TKI therapy, prompting a specific search for the T790M resistance mutation. Results:Among the 70 patients, 50% did not have available tissue-based EGFR status for various reasons (non-contributory samples, lack of material, etc.), and none had undergone tissue testing for the T790M mutation. Of the 62 patients tested for activating mutations (exons 18 to 21), 19 (30.6%) were EGFR-mutated, including 11 patients without a known tissue EGFR status. The mutations detected were predominantly exon 19 deletions (79%), followed by the L858R mutation (21%). Regarding the T790M resistance mutation, only one of the eight evaluated patients tested positive. Two false-negative cases were observed, where EGFR mutations were detected on tissue but not on plasma. The concordance rate between tissue and plasma testing was 94.29%, with a sensitivity of 88.89% and a specificity of 100%. Liquid biopsy-based molecular analysis enabled 18 patients to receive TKI therapy, including 10 in the first-line setting. It also allowed immunotherapy to be confidently considered in EGFR wild-type patients. Conclusion: Liquid biopsy represents a valuable complement, and in some cases an alternative, to tissue biopsy for the detection of EGFR mutations in NSCLC. It offers a reliable, rapid, and minimally invasive molecular evaluation, contributing to a more personalized and optimized patient management. These findings support the need for broader implementation of liquid biopsy in clinical practice