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Lao Saal
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EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.14-16 - Use of Digital Droplet PCR for Detecting EGFR T790M Resistance Mutation in Plasma at Progression on TKI Therapy (Now Available) (ID 2152)
08:00 - 18:00 | Author(s): Lao Saal
- Abstract
Background
Therapy surveillance is a corner stone in advanced lung cancer clinical management. Due to the ease of sampling, analysis of tumor derived circulating DNA in plasma for treatment monitoring and decision making is desirable. Patients with tumors harboring a sensitizing EGFR mutation benefit from targeted therapy using tyrosine kinase inhibitors (TKIs). Unfortunately, the majority of patients develop resistance towards the initially administered TKI either through intrinsic mechanisms of EGFR or mutations of additional genes such as amplification of MET. Osimertinib can be administered at disease progression due to the resistance mutation T790M in EGFR. In this study we used liquid biopsy at progression after TKI treatment to assess mutational status of sensitizing and T790M mutations. In some cases, a tumor biopsy was analyzed in parallel as part of clinical management.
Method
Six 10 ml Streck Cell free BCT® tubes were collected and plasma was isolated. Cell free circulating DNA was purified and used in an ultra-sensitive ddPCR assay IBSAFE (George et al, manuscript in preparation). Both the sensitizing EGFR mutation and T790M was analyzed. In some cases, a solid biopsy was analyzed in the clinic in parallel to our plasma analysis. Patient outcome data will be collected from patient files.
Result
Eighteen of 25 patients tested positive in plasma for the previously known sensitizing EGFR mutation (72%). Twelve of 25 tested positive in plasma for T790M mutation (48%). Among plasma samples positive for the sensitizing mutation, 67% were also positive for T790M. The minor allele frequency (MAF) fraction of T790M in comparison to the sensitizing mutation varied extensively from 0.01% to 90% and also the MAF compared to total DNA varied (0.005% to 23%). Updated clinical follow up data will be presented.
Conclusion
For a subset of patients were a tumor biopsy is not feasible, a liquid biopsy could provide information about the mutational status. As the MAF vary considerably and can be very low, a highly sensitive assay such as the IBSAFE ddPCR assay, capable of confirming a mutation at a MAF as low as 0.005% is advantageous. Further, a large plasma input volume may aid in identifying patients positive for mutations at a low MAF. Updated clinical follow up data will be discussed.
