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Summary
INTRODUCTION: Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated NSCLC who have been pre-treated with EGFR-TKIs. We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in clinical routine. METHODS: From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated NSCLC who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital PCR (ddPCR) in all patients and by tissue analyses in selected patients. RESULTS: T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine out of the 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% CI 8.1-12.1). Median survival was not reached and the 1-year survival was 64%. The response rate (RR) was 70% in T790M-positive patients (n=91) in the intention-to-treat population. PFS trended to be longer in patients with low T790M copy number (<10 copies/mL) compared to those with high T790M copy number (>/=10 copies/mL) (hazard ratio [HR] for PFS 1.72, 95% confidence interval [CI] 0.92-3.2, p=0.09). A comparable trend was observed for overall survival (HR for OS 2.16, 95% CI 0.89-5.25, p=0.09). No difference in RR was observed based on T790M copy numbers. CONCLUSIONS: Plasma genotyping using ddPCR is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib.
