Biological impact of chemotherapy during treatment with EGFR tyrosine kinase inhibitors for non-small cell lung cancer positive for EGFR activating mutations

作者：Eiji Iwama, Kazuko Sakai, Taishi Harada, Shintaro Kanda, Shunichi Sugawara, Toshihide Yokoyama, Hirokazu Taniguchi, Kaoru Tanaka, Ryo Toyozawa, K. Koyama, Yoshitaka Zenke, Gen Kida, Yasuhiko Nishioka, Hiroshi Yokouchi, Masayuki Hirose, Kazuto Nishio, Nobuyuki Yamamoto, Yuichiro Ohe, Isamu Okamoto · 发表于：Lung Cancer · 年份：2025 · DOI：10.1016/j.lungcan.2025.108756 · 被引用次数：3 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Immunotherapy and Biomarkers、HER2/EGFR in Cancer Research

BACKGROUND: The aim of this study was to explore the biological impact of chemotherapy during epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in individuals with non-small cell lung cancer (NSCLC). METHODS: Plasma and tumor tissue specimens were prospectively collected from NSCLC patients with EGFR activating mutations who participated in a randomized phase III study comparing EGFR-TKI therapy with or without inserted chemotherapy (JCOG1404/WJOG8214L). The specimens were analyzed for genetic mutations by droplet digital polymerase chain reaction analysis and next-generation sequencing. RESULTS: Two hundred patients were enrolled in this biomarker study, with 113 and 87 individuals receiving EGFR-TKI monotherapy and EGFR-TKI treatment plus inserted chemotherapy, respectively. Although progression-free survival (PFS) for EGFR-TKI monotherapy was shorter in patients with than in those without detectable EGFR activating mutations in cell-free DNA at baseline, inserted chemotherapy improved PFS compared with EGFR-TKI monotherapy for the former patients (median, 17.5 vs. 11.8 months). Inserted chemotherapy suppressed the number of alleles positive for activating and T790M mutations of EGFR in cell-free DNA at disease progression. The benefit of inserted chemotherapy relative to EGFR-TKI monotherapy was more apparent in patients with (median PFS, 18.8 vs. 13.5 months) than in those without detectable concurrent mutations of TP53. CONCLUSIONS: Chemot...