BACKGROUND: Epidermal growth factor receptor (EGFR) T790M mutation drives acquired drug resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant lung cancer. However, it was reported that this mutation may exist before drug exposure. The objective of the current study was to evaluate whether the clinical outcomes are affected by the percentage of preexisting T790M mutations within a tumor. METHODS: Pretreatment tissues were collected from 124 patients with advanced non-small cell lung cancer with sensitizing EGFR mutations that were detected by direct sequencing. Genotyping for EGFR T790M mutation was further performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patients who were positive for the T790M mutation were divided to 2 subgroups according to T790M mutant signal frequency. RESULTS: The T790M mutation was found in 31 patients (25.0%). The T790M mutation frequency at which the risk of disease progression after therapy with EGFR-TKIs begins to increase was estimated to be 3.2%. The patients with T790M-positive tumors had a shorter time to disease progression after treatment with EGFR-TKIs (median, 6.3 months vs 11.5 months; P < .001) and overall survival (median, 16.1 months vs 26.5 months; P = .065) compared with those with T790M-negative tumors. Among the T790M-positive patients, the patients with high T790M frequency (9 patients) were found to have a shorter time to disease progression (median, 2.4 months vs 6.7 months; P = .009) and overall survival (median, 9.1 months vs 18.7 months; P = .018) compared with those with low T790M frequency (22 patients). CONCLUSIONS: A preexisting EGFR T790M mutation was noted in 25% of patients with EGFR-mutant lung cancer. Patients with a high T790M mutation frequency had worse clinical outcomes to EGFR-TKIs than patients with a low T790M mutation frequency.
BACKGROUND:Epidermal growth factor receptor (EGFR) T790M mutation drives acquired drug resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant lung cancer. However, it was reported that this mutation may exist before drug exposure. The objective of the current study was to evaluate whether the clinical outcomes are affected by the percentage of preexisting T790M mutations within a tumor. METHODS: Pretreatment tissues were collected from 124 patients with advanced non-small cell lung cancer with sensitizing EGFR mutations that were detected by direct sequencing. Genotyping for EGFRT790M mutation was further performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patients who were positive for the T790M mutation were divided to 2 subgroups according to T790M mutant signal frequency. RESULTS: The T790M mutation was found in 31 patients (25.0%). The T790M mutation frequency at which the risk of disease progression after therapy with EGFR-TKIs begins to increase was estimated to be 3.2%. The patients with T790M-positive tumors had a shorter time to disease progression after treatment with EGFR-TKIs (median, 6.3 months vs 11.5 months; P < .001) and overall survival (median, 16.1 months vs 26.5 months; P = .065) compared with those with T790M-negative tumors. Among the T790M-positive patients, the patients with high T790M frequency (9 patients) were found to have a shorter time to disease progression (median, 2.4 months vs 6.7 months; P = .009) and overall survival (median, 9.1 months vs 18.7 months; P = .018) compared with those with low T790M frequency (22 patients). CONCLUSIONS: A preexisting EGFRT790M mutation was noted in 25% of patients with EGFR-mutant lung cancer. Patients with a high T790M mutation frequency had worse clinical outcomes to EGFR-TKIs than patients with a low T790M mutation frequency.
Authors: Aaron N Hata; Harald Paganetti; Clemens Grassberger; David McClatchy; Changran Geng; Sophia C Kamran; Florian Fintelmann; Yosef E Maruvka; Zofia Piotrowska; Henning Willers; Lecia V Sequist Journal: Cancer Res Date: 2019-05-21 Impact factor: 12.701
Authors: Gabriele Romano; Pei-Ling Chen; Ping Song; Jennifer L McQuade; Roger J Liang; Mingguang Liu; Whijae Roh; Dzifa Y Duose; Fernando C L Carapeto; Jun Li; Jessica L F Teh; Andrew E Aplin; Merry Chen; Jianhua Zhang; Alexander J Lazar; Michael A Davies; P Andrew Futreal; Rodabe N Amaria; David Y Zhang; Jennifer A Wargo; Lawrence N Kwong Journal: Cancer Discov Date: 2018-03-01 Impact factor: 39.397
Authors: Hanyan Xu; Adam Abdul Hakeem Baidoo; Shanshan Su; Junru Ye; Chengshui Chen; Yupeng Xie; Luca Bertolaccini; Mahmoud Ismail; Biagio Ricciuti; Calvin Sze Hang Ng; Raja M Flores; Yuping Li Journal: Transl Lung Cancer Res Date: 2019-04