Abstract
Abstract Background: EGFR tyrosine kinase inhibitors (TKIs) are current standard treatments for non-small cell lung cancers (NSCLCs) with EGFR mutation. Current diagnostic tests for EGFR mutation include direct sequencing, pyrosequencing or real-time PCR based technology. We have developed a digital droplet PCR based analysis, GenesWell™ ddEGFR Mutation Test (IUO version 5.2. Gencurix Inc., Seoul, Korea). Methods: We have analyzed a total of 325 archived tissue from 233 lung cancer patients treated with gefitinib or erlotinib in the participating 3 hospitals from 2008 to 2013. Samples were analyzed with GenesWell™ ddEGFR Mutation Test and the results were compared with in-house results recorded in each institutional EMR. Results: Since we have analyzed left-over archived tissue, the amount of DNA was inappropriate for analysis in few cases (n=5, 1.5%), which had less than 2ng/uL concentration of DNA. ddEGFR test detected additional EGFR mutations in patients with EGFR wild-type (WT) (N=4), exon 19 deletion (19del) (N=4) and exon 21 L858R (L858R) (N=3) by in-house EGFR test. ddEGFR test detected EGFR mutations in cytology-base samples, such as pleural effusion or ascites. Small amount of sample from CSF and plasma was also detectable with ddEGFR test. Based on in-house EGFR mutation results, response rates (RRs) and disease control rates (DCRs) were as follows: 15.8% and 26.9% in WT, 71.4% and 91.8% in 19del, and 55.9% and 91.2% in L858R. Similarly, RRs and DCRs were as follows, based on ddEGFR results: 13.4% and 43.9% in wild-type (WT), 77.6% and 93.9% in 19del and 54.1% and 86.5% in exon 21 L858R (L858R). Mean allele frequencies were 48.6 (0 - 180.5) in PR, 27.4 (0 - 287.5) in SD, and 9.5 (0-159.6) in PD (P-value, PR vs SD: .0078, PR vs PD: <.000001, SD vs. PD: .029, respectively, Student T-test) Conclusion: The GenesWell™ ddEGFR Mutation demonstrate a high sensitivity for EGFR mutation detection. RRs and DCRs were comparable between in-house EGFR test and ddEGFR. Quantitative analysis of EGFR mutant allele could predict responses to EGFR TKIs. Plasma-based detection of EGFR mutations with ddEGFR are being tested in patients with EGFR mutant lung cancers. Supported by the R&D Program for Society of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (Grant number : 2013M3C8A1078499) Citation Format: Jin-Soo Kim, Mi Young Kim, Sung-Su Kim, Hyun-jeung Choi, Yunsu Lee, In-Seon Lee, Jin-Hyun Park, Ki Hwan Kim, Hoon Gu Kim, Bong Seog Kim, Young Kee Shin. Quantification of EGFR allele frequency predicts tumor response to EGFR tyrosine kinase inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-241. doi:10.1158/1538-7445.AM2017-LB-241
Published Version
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