T790M mutations identified by circulating tumor DNA test in lung adenocarcinoma patients who progressed on first-line epidermal growth factor receptor-tyrosine kinase inhibitors

Background: Plasma circulating tumor deoxyribonucleic acid (ctDNA) test is an alternative method to detect the T790M mutation. Compared to conventional tumor rebiopsy, ctDNA possesses several advantages including less invasive, faster, lower costs, and having minimal risk of complications for patients. Objective: The main objective of the study is to identify the prevalence of T790M mutations in lung adenocarcinoma patients who progressed after tyrosine kinase inhibitors (TKIs) therapy using ctDNA examination. Materials and Methods: This was a retrospective cohort study based on medical records of lung adenocarcinoma patients in the Oncology Outpatient Clinic of Dr. Soetomo General Hospital within the period of January 2017-June 2018. Patients who progressed after receiving first-line epidermal growth factor receptor-TKI (EGFR-TKI) undergone plasma ctDNA examination and genotyping using digital platforms (Droplet DigitalT PCR) method. Results: In total, there were 39 patients who met the criteria for ctDNA testing. Thirty-three patients (84.6%) received first-line gefitinib, while the other six (15.4%) received erlotinib. The T790M mutations were detected in 46.2% of patients. In addition, EGFR common mutation in exon 19 and exon 21 were detected in 87.2% of patients. Median progression-free survival of patients receiving first-line gefitinib or erlotinib were both around 9 months and did not differ significantly. Conclusions: CtDNA examination successfully detected T790M mutation in a certain proportion of lung adenocarcinoma patients who progressed after first-line EGFR-TKI without the need for difficult and invasive rebiopsy.