EGFR T790MMUTATION-POSITIVE FREQUENCY ANALYSIS BY DROPLET DIGITAL PCR OF PLASMA SAMPLES FROM PATIENTS WITH NSCLC

Introduction: Around 85% of lung cancer cases are non-small cell lung cancer (NSCLC), and mutations that lead to sensitivity or resistance to the treatment of this type of cancer are well described. The three most relevant EGFR mutations are: deletion at exon 19 (DEL19) and L858R, both conferring sensitivity to first generation tyrosine kinase inhibitors (TKIs), and T790M, that leads to resistance to the above mentioned inhibitors, but it is sensitive to third generation TKIs. Herein, we describe the overall frequency of these mutations in patient plasma samples. Methods: In this study, 397 reports were analyzed (data collected between April 2018 to March 2019) in order to evaluate EGFR T790M mutation-positive frequency. These reports were of liquid biopsy assays, by droplet digital PCR (ddPCR), in which EGFR DEL19, L858R, and T790M were assessed. Results: From the 397 reports, 232 (58%) were wildtype for all the three mutations tested, and 165 (42%) were positive for one or more mutations, being 66 (16,62%) positive for T790M. Analyzing only positive results (n = 165), mimicking the kind of population used in FFPE studies, T790M frequency reaches 40%, similar to what is observed on studies using plasma. Furthermore, when 207 patients from the 232 wild-type reports were searched for previous or later results, 73 (35%) had not any previous or later results, 91 (44%) had previous results (being 23 wild-type, 54 positive for DEL19 or L858R, 13 positive for other sensitivity mutations and 1 positive for T790M), and 43 (21%) had later results (30 results negative for T790M and 13 results positive for T790M 12 from FFPE samples and 1 from plasma). Discussion: These data show that, unlike patients analyzed in literature, we receive at IHP samples for the diagnostic of sensitivity mutations and also wild-type samples for these mutations (that could have been collected in a time point when there is not sufficient cfDNA), making the population evaluated by us different from the populations used in most scientific studies, which could explain the difference in T790M positivity frequencies. More samples will be analyzed in order to add greater robustness to our findings.

 

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Artikel online veröffentlicht:
23. Oktober 2019