Journal
LUNG CANCER
Volume 102, Issue -, Pages 101-107Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2016.10.015
Keywords
Lung adenocarcinoma; EGFR-TKI; p16/CDKN2A; Homozygous deletion
Categories
Funding
- National Natural Science Foundation of China [81272901]
- Open Project of State Key Laboratory of Respiratory Disease [SKLRD2016OP011]
- Science and Technology Planning Project of Guangdong Province [2014A020212340]
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Objectives: Activating mutations in the epidermal growth factor receptor (EGFR) are strongly predictive of EGFR-tyrosine kinase inhibitor (TKI) activity in non-small cell lung cancer (NSCLC). However, primary resistance to EGFR-TKIs occurs in approximately 20-30% of NSCLC patients with EGFR mutations. The goal of this study was to determine whether p16/CDKN2A homozygous deletion (HD) is associated with primary resistance to EGFR-TKIs in lung adenocarcinoma patients with EGFR activating mutations. Methods: We investigated 127 patients with stage IIIB or IV lung adenocarcinoma harboring activating EGFR mutations, and who had received EGFR-TKIs as first-line therapy. Dual-color fluorescence in situ hybridization for p16/CDKN2A and chromosome 9 was performed in tumor biopsy samples obtained before initiation of EGFR-TKI treatment. Results: p16/CDKN2A HD was detected in 24.4% (31/127) of patients, and the overall response rate in patients with and without this mutation was 48.4% and 78.1%, respectively (P = 0.0027). The median progression-free survival was 5.3 months (95% confidence interval [CI]: 4.582-6.018) for patients with p16/CDKN2A HD and 10.5 months (95% CI: 9.365-11.635 months) for patients without the mutation (P = 0.001). No correlations between p16/CDKN2A HD and patient characteristics including gender, age, smoking history, EGFR mutation type, tumor-node-metastasis stage, and performance status were found. Conclusions: Our study demonstrates that the coexistence of p16/CDKN2A HDs and activating EGFR mutations in lung adenocarcinoma patients signifies a poor response to EGFR-TKI therapy. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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