Dataset Information

Serial Plasma Cell-Free Circulating Tumor DNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in EGFR T790M-Positive NSCLC.

ABSTRACT:

Introduction

Recent advances in the detection of genomic DNA from plasma samples allow us to follow tumor DNA shedding in plasma during systemic treatment. Osimertinib is the standard of care for patients with NSCLC with acquired EGFR T790M mutations. We assessed changes in serial plasma cell-free circulating tumor DNA (ctDNA) genomic alterations to predict osimertinib efficacy.

Methods

We prospectively collected plasma from patients having EGFR-mutated advanced NSCLC previously treated with EGFR tyrosine kinase inhibitor therapy and with acquired EGFR T790M mutation detected by standard methods. Plasma samples were collected before starting osimertinib treatment, 4 weeks after osimertinib treatment, and on progression. ctDNA was analyzed using the Guardant360 assay.

Results

A total of 15 eligible patients received osimertinib. Before starting treatment, EGFR-activating mutations were detected in the ctDNA of all patients, and EGFR T790M was detected in 93% of the cases. Osimertinib treatment was associated with an objective response rate of 53% and a median progression-free survival of 7.3 months. A total of 12 of the 15 patients had undetectable plasma T790M and decreased activating mutation allelic frequency (AF) at week 4. None of the 12 patients had disease progression within 16 weeks. For the remaining three patients, with detectable plasma T790M (n = 2) or increased activating mutation AF (n = 1) at week 4, two had progressive disease within 16 weeks (p = 0.03).

Conclusions

In patients with EGFR-mutated advanced NSCLC, persistent EGFR T790M or increasing activating mutation AF as detected in ctDNA 4 weeks after the start of osimertinib treatment may predict disease progression within 16 weeks.

SUBMITTER: Liao BC

PROVIDER: S-EPMC8474212 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Serial Plasma Cell-Free Circulating Tumor DNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in <i>EGFR</i> T790M-Positive NSCLC.

Liao Bin-Chi BC Hsu Wei-Hsun WH Lee Jih-Hsiang JH Yang Ching-Yao CY Tsai Tzu-Hsiu TH Liao Wei-Yu WY Ho Chao-Chi CC Lin Chia-Chi CC Shih Jin-Yuan JY Yu Chong-Jen CJ Soo Ross A RA Yang James Chih-Hsin JC

JTO clinical and research reports 20200919 1

<h4>Introduction</h4>Recent advances in the detection of genomic DNA from plasma samples allow us to follow tumor DNA shedding in plasma during systemic treatment. Osimertinib is the standard of care for patients with NSCLC with acquired <i>EGFR</i> T790M mutations. We assessed changes in serial plasma cell-free circulating tumor DNA (ctDNA) genomic alterations to predict osimertinib efficacy.<h4>Methods</h4>We prospectively collected plasma from patients having <i>EGFR</i>-mutated advanced NSCL ...[more]

PMID: 34589970

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