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Bryan C Ulrich
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P34 - Pathology - Liquid Biopsy (ID 104)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P34.04 - Circulating Tumor DNA (ctDNA) as a Marker of Progressive Disease in Patients with Advanced Lung Cancer (ID 3421)
00:00 - 00:00 | Presenting Author(s): Bryan C Ulrich
- Abstract
Introduction
ctDNA is a novel, non-invasive biomarker that is increasingly investigated and used in the care of patients with cancer. Early applications of this technology relied on its ability to identify the presence of clinically actionable mutations, e.g. the detection of EGFR sensitizing mutation at diagnosis. Recently, there has been growing interest in whether the longitudinal kinetics of this biomarker can predict clinically meaningful endpoints. Ongoing studies are investigating its potential role as a surrogate biomarker of response. However, its ability to predict progression has not been thoroughly investigated, outside of anecdotal data that EGFR T790M concentration levels rise earlier than radiographic progression in some patients progressing on erlotinib. Here, we investigate ctDNA’s ability to predict radiographic progression in advanced lung cancer patients receiving third-generation EGFR TKIs.
Methods
Three early-stage clinical trials of third-generation EGFR inhibitors performed at our institution in which patients underwent routine plasma monitoring and standard imaging were studied. Forty patients with detectable EGFR sensitizing mutation (L858R=27.5%; Exon 19 Deletion= 72.5%) in plasma at baseline were analyzed. All patients had stage IV non-small cell lung cancer (NSCLC) and had experienced past progression on EGFR TKI; 92.5% of patients had histopathology-confirmed EGFR T790M mutation at the start of trial. Retrospective analysis was performed to identify date of progressive disease (as defined by RECIST1.1 criteria). ctDNA was assessed via digital droplet PCR and analyzed to identify the date of “plasma progression”, defined as any rise of EGFR sensitizing mutation relative to the prior draw or lack of at least a 50% decrease in ctDNA concentration by the first day of cycle two (21-day cycles).
Results
Plasma progression was identified at or before radiographic progression in thirty-three of forty patients (82.5%). Of the ten patients with CNS only progression, plasma progression was identified in 60% of those at or before radiographic progression. Of the thirty patients who had non-CNS progression, plasma progression was identified in 90% of those at or before radiographic progression. Plasma progression occurred at a median of 0.95 months (Range: 0-9.7 months) before radiographic progression in our cohort. Of thirty-two plasma progression events called where a subsequent ctDNA draw was available in the absence of clinical change between results, there were only five “false positives” where the subsequent draw had undetectable ctDNA.
Conclusion
These data identify the rise in circulating tumor DNA, “plasma progression”, as a strong predictor of radiographic progressive disease in patients with EGFR mutant NSCLC undergoing targeted therapy with third generation TKIs. Plasma progression was highly sensitive at capturing radiographic progression in non-CNS progression, though its lower performance overall in the subset of patients with CNS only progression is consistent with prior data of low systemic ctDNA shed among CNS tumors (both primary and metastatic). These data lay the groundwork for future studies including the incorporation of ctDNA kinetics into routine clinical care, especially to identify and/or inform progressive disease. Further investigation into early plasma progression relative to radiographic progression may harbour interesting insights about mechanisms of resistance.
