期刊
JOURNAL OF THORACIC ONCOLOGY
卷 13, 期 11, 页码 1668-1675出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtho.2018.07.016
关键词
EGFR; PD-1; PD-L1; De novo resistance; NSCLC
资金
- National Key R&D Program of China [2016YFC1303800]
- Key Lab System Project of Guangdong Science and Technology Department - Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer [2012A061400006, 2017B030314120]
- Special Fund of Public Interest by National Health and Family Control Committee [201402031]
- General Research Project of Guangzhou Science and Technology Bureau [201607010391]
Introduction: This study evaluated whether tumor expression of programmed death ligand 1 (PD-L1) could predict the response of EGFR-mutated NSCLC to EGFR tyrosine kinase inhibitor (TKI) therapy. Methods: We retrospectively evaluated patients who received EGFR-TKIs for advanced NSCLC at the Guangdong Lung Cancer Institute between April 2016 and September 2017 and were not enrolled in clinical studies. The patients' EGFR and PD-L1 statuses were simultaneously evaluated. Results: Among the 101 eligible patients, strong PD-L1 expression significantly decreased objective response rate, compared with weak or negative PD-L1 expression (35.7% versus 63.2% versus 67.3%, p = 0.002), and shortened progression-free survival (3.8 versus 6.0 versus 9.5 months, p < 0.001), regardless of EGFR mutation type (19del or L858R). Furthermore, positive PD-L1 expression was predominantly observed among patients with de novo resistance rather than acquired resistance to EGFR-TKIs (66.7% versus 30.2%, p = 0.009). Notably, we found a high proportion of PD-L1 and cluster of differentiation 8 (CD8) dualpositive cases among patients with de novo resistance (46.7%, 7 of 15). Finally, one patient with de novo resistance to EGFR-TKIs and PD-L1 and CD8 dual positivity experienced a favorable response to anti-programmed death 1 therapy. Conclusions: This study revealed the adverse effects of PD-L1 expression on EGFR-TKI efficacy, especially in NSCLC patients with de novo resistance. The findings indicate the reshaping of an inflamed immune phenotype characterized by PD-L1 and CD8 dual positivity and suggest potential therapeutic sensitivity to programmed death 1 blockade. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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