Dataset Information

A large-scale, multicentered trial evaluating the sensitivity and specificity of digital PCR versus ARMS-PCR for detecting ctDNA-based EGFR p.T790M in non-small-cell lung cancer patients.

ABSTRACT:

Background

Developing liquid biopsy technology with higher sensitivity and specificity especially for low-frequency mutations remains crucial. This study demonstrated superior performance of the newly developed digital PCR (dPCR) kit for ctDNA-based EGFR p.T790M detection in metastatic non-small-cell lung cancer (NSCLC) against ARMS-PCR.

Methods

This large-scale, multi-centered diagnostic study recruited 1,045 patients including 1,029 patients diagnosed with advanced NSCLC and 16 patients with specific samples between April 1^st 2018 and November 30^th 2019. EGFR p.T790M in plasma samples from mNSCLC patients were tested using dPCR with ADx-ARMS PCR and Cobas^® EGFR Mutation Test V2 as comparator assays to confirm cut-off value for dPCR and evaluate its performance against ARMS-PCR-based assays. Efficacy was evaluated for patients with EGFR p.T790M detected by dPCR or ARMS-PCR, who underwent Osimertinib treatment.

Results

The sensitivity, specificity, and concordance of dPCR against ADx-ARMS PCR was 98.15%, 88.66% and 90.16%, respectively for 1,026 plasma samples. Additional 9.26% patients were detected positive by dPCR. The majority of those samples had a mutation allele frequency between 0.1% and 1%. In 45 paired tissue and plasma samples, the sensitivity improved from 30.77% to 53.85% by dPCR with the specificity over 90%. The response of Osimertinib in 74 EGFR p.T790M-positive patients detected by dPCR, including 26 determined as negative by ARMS-PCR, were evaluated to have an ORR of 44.59% and a DCR of 90.54%.

Conclusions

dPCR is a sensitive and accurate tool for ctDNA-based EGFR p.T790M detection due to its significantly improved sensitivity without compromising specificity, and dPCR is equivalent to ARMS-PCR as a companion diagnostic tool while benefiting more patients under Osimertinib treatment.

Trial registration

Chinese Clinical Trial Registry identifier: ChiCTR2100043147.

SUBMITTER: Xu J

PROVIDER: S-EPMC8577974 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

A large-scale, multicentered trial evaluating the sensitivity and specificity of digital PCR versus ARMS-PCR for detecting ctDNA-based <i>EGFR</i> p.T790M in non-small-cell lung cancer patients.

Xu Jiachen J Wu Wei W Wu Chunyan C Mao Yong Y Qi Xiaowei X Guo Lin L Lu Renquan R Xie Shuhong S Lou Jiatao J Zhang Yu Y Ding Yiyan Y Guo Zijian Z Zhang Li L Liang Naixin N Chen Peng P Zhang Cuicui C Tao Min M Yu Zhengyuan Z Geng Hua H Xu Meilin M Shi Meiqi M Wang Li L Guo Wei W Zhao Jun J Li Jianjie J Shi Lixia L Zhang Yan Y Qin Zhonghua Z Chen Jun J Liu Jinghao J Ren Jing J Yang Zhenlin Z Pan Xin X Lv Zhaoqing Z Dong Hao H Zhang Jie J Ou Jiajia J Li Zhaoliang Z Kaji Kavanaugh K Wang Yan Y Wang Jie J Wang Zhijie Z

Translational lung cancer research 20211001 10

<h4>Background</h4>Developing liquid biopsy technology with higher sensitivity and specificity especially for low-frequency mutations remains crucial. This study demonstrated superior performance of the newly developed digital PCR (dPCR) kit for ctDNA-based <i>EGFR</i> p.T790M detection in metastatic non-small-cell lung cancer (NSCLC) against ARMS-PCR.<h4>Methods</h4>This large-scale, multi-centered diagnostic study recruited 1,045 patients including 1,029 patients diagnosed with advanced NSCLC ...[more]

PMID: 34858779

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