Changes in the concentration of EGFR-mutated plasma DNA in the first hours of targeted therapy allow the prediction of tumor response in patients with EGFR-driven lung cancer

• DOI: 10.1007/s10147-022-02128-6
• Publication Date: 2022-02-16T11:02:56Z
• Authors: Fedor V. Moiseyenko; Ekaterina S. Kuli...; Albina S. Zhabina; Sergey A. Belukhin; Tatiana A. Laidus; Aleksandr S. Mart...; Kirill A. Zagorodnev; Tatyana N. Sokolova; Svetlana A. Chuin...; Maxim M. Kholmatov; Elizaveta V. Arte...; Ekaterina O. Step...; Tatiana N. Shuginova; Nikita M. Volkov; Grigoriy A. Yanus; Evgeny N. Imyanitov
• Keywords: ErbB Receptors; 03 medical and health sciences; Lung Neoplasms; 0302 clinical medicine; Carcinoma, Non-Small-Cell Lung; Mutation; Humans; Original Article; Protein Kinase Inhibitors; Circulating Tumor DNA; 3. Good health

This study aimed to analyze changes in the plasma concentration of EGFR-mutated circulating tumor DNA (ctDNA) occurring immediately after the start of therapy with EGFR tyrosine kinase inhibitors (TKIs).Serial plasma samples were collected from 30 patients with EGFR-driven non-small cell lung cancer before intake of the first tablet and at 0.5, 1, 2, 3, 6, 12, 24, 36 and 48 h after the start of the therapy. The content of EGFR alleles (exon 19 deletions or L858R) in ctDNA was measured by ddPCR.ctDNA was detected at base-line in 25/30 (83%) subjects. Twelve (50%) out of 24 informative patients showed > 25% reduction of the ctDNA content at 48 h time point; all these patients demonstrated disease control after 4 and 8-12 weeks of therapy. The remaining 12 individuals showed either stable content of EGFR-mutated ctDNA (n = 5) or the elevation of ctDNA concentration (n = 7). 10 of 12 patients with elevated or stable ctDNA level achieved an objective response at 4 weeks, but only 5 of 10 evaluable patients still demonstrated disease control at 8-12 weeks (p = 0.032, when compared to the group with ctDNA decrease). The decline of the amount of circulating EGFR mutant copies at 48 h also correlated with longer progression-free survival (14.7 months vs. 8.5 months, p = 0.013).Comparison of concentration of EGFR-mutated ctDNA at base-line and at 48 h after the start of therapy is predictive for the duration of TKI efficacy.