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Longitudinal monitoring of somatic genetic alterations in circulating cell‐free DNA during treatment with epidermal growth factor receptor–tyrosine kinase inhibitors
Author(s) -
Iwama Eiji,
Sakai Kazuko,
Hidaka Noriko,
Inoue Koji,
Fujii Akiko,
Nakagaki Noriaki,
Ota Keiichi,
Toyozawa Ryo,
Azuma Koichi,
Nakatomi Keita,
Harada Taishi,
Hisasue Junko,
Sakata Shinya,
Shimose Takayuki,
Kishimoto Junji,
Nakanishi Yoichi,
Nishio Kazuto,
Okamoto Isamu
Publication year - 2020
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.32481
Subject(s) - medicine , t790m , epidermal growth factor receptor , liquid biopsy , somatic cell , tyrosine kinase inhibitor , lung cancer , hazard ratio , tyrosine kinase , oncology , gefitinib , cancer research , cancer , receptor , gene , biology , confidence interval , genetics
Background The aim of this study was to evaluate the potential of liquid biopsy for prediction of the efficacy of epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) treatment and for assessment of the changes in genetic alterations during such treatment. Methods Plasma samples were prospectively collected from non–small cell lung cancer patients with EGFR ‐activating mutations during EGFR‐TKI treatment until disease progression and were analyzed for such mutations with droplet digital polymerase chain reaction and for other somatic alterations with next‐generation sequencing. Results One hundred patients, including 87 who were EGFR‐TKI naïve, were enrolled. Median progression‐free survival was significantly shorter for EGFR‐TKI–naïve patients with EGFR ‐activating mutations detected in plasma at baseline than for those without them (7.9 vs 19.0 months; P < .001), with the values being significantly longer for initially positive patients who became negative for these mutations at 12 or 24 weeks than for those who remained positive. An increase in the number of alleles positive for EGFR ‐activating mutations in plasma during treatment was associated with disease progression, with a hazard ratio of 4.72 (95% CI, 2.07‐10.79; P < .001) for EGFR‐TKI–naïve patients showing an increase within 36 weeks. For 55 patients with available samples, the total number of somatic alterations (other than activating mutations or T790M of EGFR ) in plasma was higher at disease progression than at baseline (33 vs 19; P = 0.04). Conclusion Liquid biopsy shows potential for prediction of EGFR‐TKI efficacy and elucidation of clonal tumor evolution during targeted therapy.