Oncotarget

Research Papers:

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

Jacky Yu-Chung Li _, James Chung-Man Ho and Kam-Hung Wong

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Oncotarget. 2018; 9:27929-27939. https://doi.org/10.18632/oncotarget.25332

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Abstract

Jacky Yu-Chung Li1, James Chung-Man Ho2 and Kam-Hung Wong1

1Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR

2Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR

Correspondence to:

Jacky Yu-Chung Li, email: lyc053@ha.org.hk

Keywords: adenocarcinoma; lung carcinoma; osimertinib; ddPCR; mutant copy number

Received: December 18, 2017     Accepted: March 24, 2018     Published: June 15, 2018

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.


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