Elsevier

Annals of Oncology

Volume 28, Issue 4, April 2017, Pages 784-790
Annals of Oncology

Original articles
Thoracic tumors
Osimertinib benefit inEGFR-mutant NSCLC patients withT790M-mutation detected by circulating tumour DNA

https://doi.org/10.1093/annonc/mdx017Get rights and content
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ABSTRACT

Background

Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by theT790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib whenT790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advancedEGFR-mutant NSCLC patients.

Material and methods

ctDNAT790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. ProgressingT790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage ofT790M positive inctDNA.

Results

ThectDNAT790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4–NA), with 6- and 12-months PFS of 66.7% and 52%, respectively.

Conclusion(s)

ctDNA from liquid biopsy can be used as a surrogate marker forT790M in tumour tissue.

Key words

EGFR mutation
T790M
osimertinib
lung cancer
ctDNA liquid biopsies

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