The T790M resistance mutation in EGFR is only found in cfDNA from erlotinib-treated NSCLC patients that harbored an activating EGFR mutation before treatment

• Published in: BMC cancer 2018-02, Vol.18 (1), p.191-191, Article 191
• Main Authors: Demuth, Christina, Madsen, Anne Tranberg, Weber, Britta, Wu, Lin, Meldgaard, Peter, Sorensen, Boe Sandahl
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Amino Acid Substitution; Analysis; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor; Carcinoma; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Care and treatment; Cell Line; Cell-Free Nucleic Acids; Cohort Studies; Complications and side effects; Development and progression; Disease Progression; Dosage and administration; Drug resistance; Drug Resistance, Neoplasm - genetics; Epidermal growth factor; Epidermal growth factors; Erlotinib; Erlotinib Hydrochloride - pharmacology; Erlotinib Hydrochloride - therapeutic use; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; Mutation; Neoplasm Grading; Neoplasm Staging; Non-small cell lung; Non-small cell lung cancer; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Receptor; Receptor, Epidermal Growth Factor - genetics
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-018-4108-0

Lung cancer patients with an activating mutation in the EGFR (epidermal growth factor receptor) can develop resistance to erlotinib treatment, which is often mediated by the T790M resistance mutation in EGFR. The difficulties in obtaining biopsies at progression make it challenging to investigate the appearance of the T790M mutation at progression in large patient cohorts. We have used cell free DNA (cfDNA) from patients treated with erlotinib to investigate if the development of a T790M mutation coincides with the presence of an activating EGFR mutation in the pre-treatment blood sample. A cohort of 227 NSCLC (non-small cell lung cancer) adenocarcinoma patients was treated with erlotinib irrespective of EGFR-mutational status. Blood samples were drawn immediately before erlotinib treatment was initiated and again at progression. The cobas® EGFR Mutation Test v2 designed for cfDNA was used to identify 42 EGFR mutations. Of the 227 NSCLC patients, blood samples were available from 144 patients both before erlotinib treatment and at progression (within 1 month before or after clinical progression). One hundred and twenty-eight of the 144 were wild-type EGFR before treatment, and we demonstrate that the T790M mutation was not present at progression in any of these. In contrast, in the 16 patients with an activating EGFR mutation in the pre-treatment blood sample six patients (38%) were identified with a T790M mutation in the progression blood sample. The T790M resistance mutation is only found in the cfDNA of erlotinib-treated NSCLC patients if they have an activating EGFR mutation before treatment.