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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
P1.01-27 - Serial Circulating Tumor DNA (ctDNA) Analysis of Blood and Saliva Predicts Osimertinib Response and Resistance in EGFR-Mutant NSCLC (ID 2909)
09:45 - 18:00 | Author(s): Wei Liao
ctDNA has emerged as a promising non-invasive tool to detect lung cancer associated genomic alterations. We assessed whether serial ctDNA monitoring of plasma and saliva correlates with tumor burden and predicts response, resistance, and progression free survival to osimertinib, the 3rd generation EGFR TKI during treatment of EGFR mutated NSCLC.Method
Plasma and saliva samples were collected at every clinic visit from patients with metastatic EGFR mutant NSCLC enrolled in a clinical trial of local ablative therapy (LAT) upon oligoprogression (5 or less sites of progression) on osimertinib (NCT02759835). Plasma ctDNA was analyzed by droplet-digital PCR (ddPCR) EGFR mutation detection and InVisionSeq Tagged-Amplicon next-generation sequencing. Saliva ctDNA was analyzed by Electric Field-Induced Release and Measurement (EFIRM) liquid biopsy (eLB) assay. Tumor burden was assessed by volumetric CT scoring of all target lesions and other soft tissue lesions ≥10 mm. ctDNA-level changes were correlated with clinical response.Result
We analyzed 389 plasma samples from 20 patients by ddPCR, 126 plasma samples from 16 patients by NGS and 298 saliva samples from 18 patients by eLB. A high correlation between ddPCR and NGS allele frequencies (AFs) was found (Spearman g=0.96; p<0.001). Plasma ddPCR and NGS also correlated with saliva eLB assay for mutant EGFR detection (Spearman g=0.42 and 0.45, respectively; p<0.001 for both). Among 14 patients who progressed, ctDNA progression (AFs increased two consecutive times by ddPCR) predated RECIST progression by a median of 87 days (range: 28-216 days) in 8 patients. Of 6 patients without ctDNA progression, 2 patients had increase in EGFR mutation-level by eLB and 1 patient by NGS. ctDNA clearance on day 42 or 56 (2 cycles of osimertinib treatment) predicted PFS (HR=0.22, 95% CI=0.06-0.79, p=0.02; figure 1). Both baseline sensitizing EGFR mutation AF and copy number, but not baseline tumor volume, were significantly associated with PFS. Acquisition of MET, EGFR, and ERBB2 amplifications and the EGFR C797S mutation were identified as key resistance mechanisms by NGS in this cohort of patients.
Serial assessment of plasma and saliva ctDNA is clinically useful for monitoring the therapeutic response to osimertinib and for early detection of resistance mechanisms for clinical decision making. Three assays used in this study, the ddPCR and NGS for plasma ctDNA detection, and eLB for saliva ctDNA detection are complementary with each having unique advantages.