Detection of epidermal growth factor receptor mutations in circulating tumor DNA: reviewing BENEFIT clinical trial

The identification of epidermal growth factor receptor (EGFR) sensitizing mutations plays a key role in the management of non-small cell lung cancer (NSCLC) patients (1-4). Tissue specimens are not always available, due to difficulty in obtaining enough material, despite the fact that more than 70% of NSCLC patients are diagnosed in the metastatic stage (5,6) due to multiple reasons. In this setting, prior to the administration of any biological or chemotherapy treatment regimen, liquid biopsy could represent a valid alternative to tissue specimens, taking in consideration the need to use appropriate molecular techniques. In addition, after treatment with first and/or second-generation tyrosine kinase inhibitors (TKIs), the arising of EGFR resistance mutations (in particular the EGFR exon 20 p.T790M) allows the treatment with third generation TKI (e.g., osimertinib) (7). Moreover, the collection of new tissue specimens after a first line treatment to detect EGFR resistance mutations and other druggable genetic alteration is challenging and time consuming. For these reasons, the European Medicines Agency (EMA) and Food and Drug Administration (FDA) approved the analysis of EGFR status on circulating tumor DNA (ctDNA) extracted from plasma samples in new NSCLC patients without tissue availability or after resistance to first and/or generation TKIs for the detection of EGFR exon 20 p.T790M (8,9)