T790M mutant copy number quantified via ddPCR predicts outcome after osimertinib treatment in lung cancer

Abstract

Osimertinib prolongs progression-free survival (PFS) in patients with metastatic, epidermal growth factor receptor (EGFR) T790M-mutated, non-small cell lung cancer (NSCLC) after failure of EGFR tyrosine kinase inhibitor (TKI) therapy. We investigated the utility of T790M mutant copy number quantification in a plasma cell-free DNA (cfDNA) assay for predicting clinical outcomes of osimertinib treatment. We retrospectively examined 161 patients who underwent plasma EGFR testing using a digital droplet polymerase chain reaction (ddPCR) technique after EGFR-TKI failure. Of the 74 (46%) patients with detectable T790M mutations in plasma, 55 received osimertinib treatment. Patients who achieved partial response had a higher plasma mutant copy levels than those with progressive disease. Patients who achieved stable disease also tended to have higher plasma mutant copy levels than those with progressive disease. High mutant copy number (≥ 105 per mL of plasma) was associated with shorter PFS (median: 5.5 months vs. not reached) and overall survival (median: 9.1 months vs. NR). Quantitative measurements of T790M mutant copy number in plasma cfDNA by ddPCR thus predicted treatment response and survival outcomes after osimertinib in NSCLC patients resistant to EGFR TKI.