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K. Sakai
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-091 - Digital PCR Analysis of Plasma Cell-Free DNA as a Noninvasive Detection of the Drug Resistance Mechanisms in EGFR Mutant NSCLC (ID 2613)
09:30 - 09:30 | Author(s): K. Sakai
- Abstract
Background:
Although the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown dramatic effects against EGFR mutant non-small-cell lung cancer (NSCLC), patients demonstrate resistant by various mechanisms, such as second-site point mutation that substitutes methionine for threonine at position 790 (T790M) in EGFR, and amplification of mesenchymal-epithelial transition (MET) proto-oncogene and human epidermal growth factor receptor 2 (HER2). With the development of overcoming resistance to EGFR-TKIs, identification of the mechanisms of drug resistance is urgently needed. However, tumor samples for detecting the resistant mechanisms were not easily available in patients with EGFR mutation-positive NSCLC relapsed after EGFR-TKIs treatment. Here, we examined the correlation of T790M mutation, activating EGFR mutations, HER2 amplification, and MET amplification in relapsed NSCLC patients between plasma and tumor samples using digital PCR assay as an alternative and noninvasive method.
Methods:
A total of 18 patients obtained pairs of tumor and blood samples after resistance to EGFR-TKI treatment were enrolled in this study. T790M mutation, activating EGFR mutations, MET amplification, and HER2 amplification in relapsed NSCLC patients after EGFR-TKIs treatment were analyzed by digital PCR.
Results:
Digital PCR analysis of T790M mutation in plasma had a sensitivity of 81.8% and specificity of 85.7%, with the overall concordance between plasma and tissue samples 83.3%. Analysis of primary active mutation in plasma showed inconsistent results with lower sensitivity of 66.7% and concordance of 70.6% compared to those of T790M mutation. MET gene copy number gain of tumor DNA by digital PCR was observed in three patients. Of these patients, one patient exhibited positive for MET amplification by FISH, whereas no patient demonstrated MET and HER2 copy number gain in plasma DNA.
Conclusion:
Digital PCR analysis in plasma is feasible and accurate method for detecting the T790M mutation in NSCLC resistance to EGFR-TKIs treatment.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-032 - Clinical Applications of Next Generation Sequencing on Therapeutic Decision-Making in Lung Cancer (ID 1007)
09:30 - 09:30 | Author(s): K. Sakai
- Abstract
Background:
The identification of driver mutations, such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), have already been successfully translated into clinical practice. The clinical implementation of genomic profiling for NSCLC with high-throughput and multiplex genotyping tests is thus warranted in order to prioritize appropriate therapies for individual patients.
Methods:
The present study has recruited lung cancer patients at Kinki University Hospital from June 2013. To screen patients with lung cancer for genetic alterations relevant to novel molecular-targeted therapeutics, we have applied a Ion AmpliSeq RNA Fusion Lung Cancer Research Panel to detect known fusion transcripts such as ALK, ROS1, RET, and NTRK1 rearrangements simultaneously in a RNA sample obtained from FFPE lung cancer tissues. Deep sequencing was also performed using the Ion AmpliSeq Colon and Lung Cancer Panel. There were two co-primary endpoints for this study. First, we assessed the percentage of patients with additional therapy options uncovered by detecting potentially actionable genetic alterations. Second, we evaluated the percentage of patients who actually received genotype-directed therapy.
Results:
From June 2013, one hundred ten patient tumor samples were sequenced with these assays, and 104 (95%) patients received the results of Ion AmpliSeq Colon and Lung Cancer Panel and 106 (96%) patients received the results of the Ion AmpliSeq RNA Fusion Lung Cancer Research Panel with a >90% success rate for genotyping. An actionable driver alteration was detected in 43 (39%) of tumors from patients, leading to use of a targeted therapy in 23 (21%).
Conclusion:
Multiplexed genomic testing can aid physicians in matching patients with targeted treatments and appropriate clinical trials.
