• Lung Cancer · Nov 2014

    Reduced chemotherapy sensitivity in EGFR-mutant lung cancer patient with frontline EGFR tyrosine kinase inhibitor.

    • Zhu Zeng, Hong-hong Yan, Xu-chao Zhang, Wen-zhao Zhong, Yan-yan He, Jin-lin Guan, Fei-yu Niu, Zhi Xie, Yi-sheng Huang, Chong-rui Xu, Song Dong, and Yi-long Wu.
    • Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Division of Thoracic Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
    • Lung Cancer. 2014 Nov 1; 86 (2): 219-24.

    ObjectivesEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a standard first-line treatment for EGFR-mutant patients with non-small cell lung cancer (NSCLC). However, it remains unclear whether frontline EGFR TKIs affect subsequent chemo-sensitivity in EGFR-mutant patients. This study compared chemo-sensitivity in patients treated with post-TKI chemotherapy and first-line chemotherapy controls.Materials And MethodsThis study included 203 EGFR-mutant patients. The study group contained 68 patients treated with chemotherapy after first-line EGFR-TKI and the control group contained 135 patients who received first-line chemotherapy. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were assessed.ResultsIn study group, the RR of chemotherapy was 13.2% compared with 34.1% in the control group (P=0.002). The median PFS of chemotherapy in the control group was significantly longer than in the study group (6.9 vs. 3.9 months, P<0.001), while the RR (76.5% vs. 68.9%, P=0.259) and PFS (11.0 vs. 10.2 months) of EGFR-TKI were similar between first- and second-line treatment. Cox regression analyses indicated that prior EGFR-TKI treatment had a higher risk for disease progression during chemotherapy treatment [hazard ratio (HR)=3.06; 95% CI=2.12-4.42, P<0.001]. Median overall survival was 31.7 months in the control group and 23.5 months in the study group (P<0.001). The adjusted HR for death in the study group was 1.91 (95% CI=1.33-2.76; P<0.001).ConclusionIn EGFR-mutant patients, frontline EGFR-TKI significantly reduced the sensitivity of subsequent chemotherapy compared with that of TKI-naïve frontline chemotherapy. These findings need to be validated in further randomized trials.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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