Correlation Between Tissue and Plasmatic EGFR in CBNPC With EGFR Mutation or Predictive Factor of EGFR Mutation

Newest therapeutic breakthrough are often based on molecular analysis of tumoral tissue before treatment initiation or after emergence of resistance. Tumoral tissue is commonly obtained by biopsy. However, tumor biopsy is an invasive, scarcely repeatable and costly technics. Moreover, tumor samples, obtained by biopsy, doesn't represent tumor heterogeneity and cannot inform about tumor evolution over time.

Recent improvement have been done in detection and characterization of blood circulating tumoral DNA (ctDNA). ctDNA reach regularly the blood stream after tumoral cell apoptosis or necrosis and could be extract and sequenced by some molecular biology technics such as real time PCR (rtPCR), digital PCR (dPCR) or next generation sequencing (NGS). Interesting, Several studies demonstrate that some genomic alterations of solid cancer can be characterized after sequencing of ctDNA. Other experiments pointed that ctDNA level could be linked to tumor stage and patient prognostic.

These progress lead to the development of a new non invasive method for extraction of ctDNA called liquid biopsy (LB). LB could be useful for monitor tumoral genotype, assess tumor response to treatment and detect residual tumor cells after curative treatment. Moreover LB could be an essential method for study of tumor cells molecular alterations mechanisms during targeted cancer therapies, when clinical resistance occurs.

Non-small cell lung cancer (NSCLC) is the most frequently diagnosticated type of lung cancer. Regular first line chemotherapy is based on the use of platinum salts. However, some mutations in the EGFR gene could add sensitivity of NSCLC to tyrosine kinase inhibitors such as gefitinib, erlotinib or afatinib. Consequently, the search for molecular mutations in genome of NSCLC cells is of prior interest for patients with clinically advanced NSCLC.

Recently, some studies demonstrate that mutational EGFR status of NSCLC was sharply correlated between tumoral tissue, obtained by classical biopsy, and ctDNA, collected by liquid biopsy.

These results provide promising data encouraging the use of LB for study of NSCLC ctDNA. However some experimentations are needed to ensure these data.

For that reason, CONCORDE clinical trial will evaluate the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. EGFR status will be assessed by real time PCR (rtPCR), digital PCR (dPCR) and Next Generation Sequencing (NGS) in patients with chemotherapy naive lung carcinoma.