Performance of different methods for detecting T790M mutation in the plasma of patients with advanced NSCLC after...

Several approaches to the detection of T790M mutations in patient plasma or tissue samples have been implemented to date. The present study was designed to assess the ability of different technologies to detect the T790M mutation in plasma samples and to evaluate the relative rates of re-biopsy and subsequent patient management in a clinical setting. Data from patients with advanced NSCLC who visited the Department of Respiratory Medicine of the First Hospital Affiliated to Wenzhou Medical University between December 2014 and July 2018 were retrospectively collected. Following re-biopsy, these patients were evaluated for the presence of the T790M mutation via next-generation sequencing (NGS), amplification refractory mutation system or Roche Cobas z480 (Cobas) analyses of tissue samples. T790M mutation status in tumor tissue samples was calculated as a standard reference used to establish the sensitivity, specificity and concordance of three circulating tumor DNA detection approaches, including NGS, droplet digital PCR (ddPCR) and super amplification refractory mutation system (SuperARMS). Subsequent patient management was also recorded. In total, 287 patients with advanced non-small cell lung cancer were evaluated, of whom 55.4% (159/287) underwent tissue re-biopsy, 76.7% (122/159) underwent sequencing analysis of plasma and/or tissue samples, and 59.0% (72/122) were found to harbor the T790M mutation. The rates of plasma sample T790M detection via NGS, ddPCR and SuperARMS were 60.0, 59.3 and 60.0%, respectively. Only 32 patients with T790M mutations (44.4%, 32/72) were treated with third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), while 19 continued treatment with first-generation TKIs, 13 underwent chemotherapy, 1 switched to treatment with anlotinib, 4 succumbed to pericardial or brain metastases, and 3 were lost to follow-up. Additionally, 2 patients exhibited histological transformation from adenocarcinoma to small cell lung cancer, while 17/97 patients who were evaluated for brain metastases during treatment exhibited intracranial progression. Of these, 8 patients had been treated with osimertinib. In this study of a real-world clinical setting, fewer patients than expected underwent re-biopsy and gene sequencing. Of the tools available for the analysis of plasma samples, NGS exhibited the highest sensitivity and concordance with the results of tissue-based T790M detection strategies. It was additionally found that only a subset of patients harboring the T790M mutation were ultimately treated using third-generation EGFR-TKIs.