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Background  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.    Methods  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.    Results  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.    Conclusion  The T790M resistance mutation is only found in the cfDNA of erlotinib-treated NSCLC patients if they have an activating  EGFR  mutation before treatment.    Electronic supplementary material  The online version of this article (10.1186/s12885-018-4108-0) contains supplementary material, which is available to authorized users.

bmc cancer

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