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H. Liu
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-040 - EGFR T790M Mutation Detection and Osimertinib Treatment Response Evaluation by Liquid Biopsy in Advanced NSCLC Patients (ID 9448)
09:30 - 09:30 | Author(s): H. Liu
- Abstract
Background:
Lung cancer remains the leading cause of cancer-related death worldwide. Though most patients with EGFR activating mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs), tumors will inevitably acquire resistance to first generation EGFR TKIs. EGFR T790M mutation accounts for about 50% of these resistance cases. Droplet digital PCR (ddPCR) and cobas enables quantification of specific mutated ctDNA. In this study, these methods were used to detect and evaluate the ctDNA response after Osimertinib treatment.
Method:
In the screening period of ASTRIS (D5160C00022) study in single center, tumor and blood samples from 69 stage ⅢB-Ⅳ NSCLC patients defined as acquired resistance to first generation EGFR TKIs (Gefitinib, Elortinib or Ecotinib) were collected. The cobas® Mutation Test v2 kit was used to detect EGFR mutations in FFPE or plasma samples. Plasma T790M mutation of both Osimertinib naïve and treated patients were quantified by Droplet digital PCR (ddPCR).
Result:
The T790M mutation rate of FFPE tissue cobas, plasma cobas and plasma ddPCR testing were 54.5%, 21.3% and 30.4% respectively. Taking the FFPE tissue cobas testing as gold standard, the sensitivity and specificity of plasma ddPCR to detect T790M mutation was 66.7% and 63.6%. Taking all testing methods into account, the T790M positive rate was 52.2%. In all of the plasma cobas positive cases, T790M mutation was detected by ddPCR. In 10 tumor biopsy cobas negative cases, 3 were positive defined by ddPCR. In 23 patients received Osimertinib treatment, the OOR was 60.9%, quantification of T790M after 6 weeks of treatment decreased to very low level, no association was observed between response status and T790M mutation decrease.
Conclusion:
ddPCR is more sensitive in plama ctDNA testing and should be performed even tumor tissue biopsy yielded negative results in certain cases. Osimertinib significantly decreased plasma T790M level, but not associated with clinical response.
