Different characteristics and survival in non‐small cell lung cancer patients with primary and acquired EGFR T790M mutation

Wang, Shuyuan; Yan, Bo; Zhang, Yanwei; Xu, Jianlin; Qiao, Rong; Dong, Yu; Zhang, Bo; Zhao, Yiming; Zhang, Lele; Qian, Jie; Lü, Jun; Zhao, Ruiying; Han, Baohui

doi:10.1002/ijc.32015

Cited by 33 publications

(38 citation statements)

References 34 publications

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“…For the purpose to detect the accompanying mutations coexisted with de novo T790M mutation, two common sensitizing EGFR mutations (L858R and 19Del) and three most frequent uncommon EGFR mutations (G719A, S768I and L861Q) were detected simultaneously. Consistent with previous studies [12,14,20], we found that most de novo T790M mutation coexist with L858R mutation (75%, 3/4). De novo T790M mutation could also co-exist with 19 Del, as well as other uncommon EGFR mutations [12,20].…”

Section: Discussionsupporting

confidence: 92%

“…Consistent with previous studies [12,14,20], we found that most de novo T790M mutation coexist with L858R mutation (75%, 3/4). De novo T790M mutation could also co-exist with 19 Del, as well as other uncommon EGFR mutations [12,20]. The reason we did not nd co-existing de novo T790M and 19 Del in our study perhaps because of the small sample size and rare de novo T790M cases.…”

Section: Discussionsupporting

confidence: 92%

“…The reason we did not nd co-existing de novo T790M and 19 Del in our study perhaps because of the small sample size and rare de novo T790M cases. However, it was reported that acquired T790M mutation always coexist with 19Del [20][21][22]. Tian's study [22] reported that the ratio of allele frequency (Relative allele frequency, RAF) of the T790M mutation to the EGFR sensitizing mutation was different between the de novo and acquired T790M mutations (86.1% vs. 22.3%, P< 0.0001).…”

Section: Discussionmentioning

confidence: 99%

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Highly sensitive droplet digital PCR method for detection of de novo EGFR T790M mutation in patients with Non-small cell lung cancer

Wang

Xiao

Guo

et al. 2020

Preprint

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Background This study was aimed to investigate the allelic relation between de novo T790M and concomitant sensitizing EGFR mutations in EGFR-TKIs naïve NSCLCs and to explore whether the formalin-fixed and paraffin-embedded (FFPE) materials affect the detection of de novo T790M mutation. Methods 300 consecutive EGFR-TKI naïve NSCLCs who received surgical resection between January 2016 and June 2018 was retrospectively investigated. All the snap-frozen tumor tissues from 300 NSCLCs were screened by droplet digital PCR (ddPCR) for the detection of de novo T790M mutation. The allelic relation between de novo T790M mutation and concomitant sensitizing EGFR mutations was also investigated. Furthermore, we assessed de novo T790M mutation in paired FFPE specimens of 50 patients which included tumor tissues and paired normal lung tissues of the pretreatment NSCLCs to investigate whether FFPE materials affect the detection of de novo T790M mutation. Results The de novo T790M mutation was observed in four patients which included one patient of single de novo T790M mutation and three patients of de novo T790M mutation coexisting with L858R mutation. The incidence of de novo T790M in pretreatment NSCLCs who harboring EGFR mutations was 2.9% (4/139). All the de novo T790M mutations were detected in cis with the concomitant L858R mutations for the three NSCLCs. Our ddPCR method demonstrated that the frequency of de novo T790M mutation were ranging from 0.1% to 0.5% among 90% (45/50) of the FFPE tumor samples and 92% (46/50) of the paired FFPE adjacent normal lung samples. The frequency of de novo T790M mutation in the paired snap-frozen samples were all below 0.1%. Conclusion Our study demonstrated that most de novo T790M mutation were detected in cis with concomitant sensitizing mutations for pretreatment NSCLCs. Analytical cut-off of ddPCR assay for FFPE specimens should be validated carefully considering the possibility of FFPE-derived artificial gene mutations.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Highly sensitive droplet digital PCR method for detection of de novo EGFR T790M mutation in patients with Non-small cell lung cancer

Wang

Xiao

Guo

et al. 2020

Preprint

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“…25,28,[45][46][47] The frequency of T790M mutation was 1.39%, consistent with the results of a study from another center in China. 48 Different detection and sampling methods led to the differences in prevalence rates, owing to variations in sensitivity and specificity. We evaluated EGFR mutation status by ARMS.…”

Section: Discussionmentioning

confidence: 99%

Poor Prognosis With Coexistence Of EGFR T790M Mutation And Common EGFR-Activating Mutation In Non- Small Cell Lung Cancer

Gao

Zhao

Bao

et al. 2019

CMAR

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Previous studies have shown that the presence of EGFR T790M mutation may reduce the treatment efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer. However, little is known about the clinical features and outcomes of EGFR T790M mutation in pretreated patients with NSCLC. Patients and methods: The clinical features of EGFR-activating and T790M mutations were assessed in a large cohort of patients with EGFR-TKI-naïve NSCLC (all/EGFR mutations, n=16,347/7,687). The correlation between the pretreatment T790M mutation status and clinical outcomes was evaluated using univariate and multivariate analyses. Results: Pretreatment T790M mutation was reported in 1.39% of the patients and coexisted with an EGFR-activating or uncommon mutation. The dual EGFR T790M and common EGFR-activating mutations were more likely to be detected in lung adenocarcinoma, whereas single T790M mutation was more prevalent in non-adenocarcinomas. The presence of de novo T790M mutation correlated with reduced recurrence-free survival (RFS) in patients with NSCLC (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.67-6.79, P = 0.001). After molecular stratification, T790M mutation was shown to exert adverse effects on the RFS of EGFR 19-del group (OR 2.89, 95% CI 1.10-7.91, P = 0.028) and EGFR L858R group (OR 3.43, 95% CI 1.33-8.88, P = 0.013). Furthermore, pretreatment T790M mutation promoted tumor metastasis to different sites. Conclusion: T790M-positive tumors presented special clinical features, and the coexistence of T790M and common EGFR-activating mutations was associated with poor prognosis in patients with NSCLC.

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“…One of the main reasons to explain the extraordinary long OS in our study was that most of the patients received second-line Osimertinib and OS was calculated from the diagnosis of advanced NSCLC. One previous study found that among patients who failed former rst-or second-generation EGFR TKIs and acquired EGFR T790M mutation, Osimertinib treatment could induce a median OS of 50.4 months [29]. In addition, patients in this study were all harboring oligo-residual disease, whom are generally having more indolent disease and could have a relative longer overall survival [30].…”

Section: Discussionmentioning

confidence: 67%

The value of local consolidative therapy in Osimertinib-treated non-small cell lung cancer with oligo-residual disease

Zeng

et al. 2020

Preprint

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Background: There was no study investigating real-world utilization and outcome of LCT in Osimertinib-treated NSCLC with oligo-residual disease. This study was to analyze the clinical value of local consolidative therapy (LCT) in Osimertinib-treated non-small cell lung cancer (NSCLC) patients with oligo-residual disease. Methods: Patients receiving standard Osimertinib treatment and developing oligo-residual disease (ﬁve or fewer residual metastatic lesions) were retrospectively reviewed. Local therapies performed to the oligo-residual tumor lesions or primary lung site before Osimertinib treatment failure were considered as LCT. Results: Of 108 patients recruited, first-line and second-line Osimertinib were administered in 25 and 83 patients, respectively, while LCT was performed in 14 patients. With a median follow-up of 43.6 months, 69 patients developed progressive disease. LCT significantly improved progression-free survival (PFS) (NR vs 12.8 months, p=0.01) and was independently associated with prolonged PFS (HR=0.29, 95%CI 0.12 to 0.68, p=0.004). Patients receiving LCT had a numerically longer overall survival (OS) (85.8 vs 77.1 months, p=0.58) and after adjusting for potentially confounding factors, LCT was associated with a non-significantly prolonged OS (HR=0.37, 95%CI 0.12-1.16, p=0.089). Pattern of failure analyses indicated that progressive disease developed at the originally existed oligo-residual lesions in 76.2% of the 63 patients who didn’t receive LCT and had Osimertinib treatment failure. Of note, 7 (70%) of the 10 patients who had oligo-residual cranial disease but didn’t receive LCT, developed more than five progressive lesions in the brain, which were no longer suitable for stereotactic radiosurgery. Conclusion: Among Osimertinib-treated NSCLC patients having oligo-residual lesions, LCT could improve local control and significantly increase PFS, which need to be verified by further investigations.

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Different characteristics and survival in non‐small cell lung cancer patients with primary and acquired EGFR T790M mutation

Cited by 33 publications

References 34 publications

Highly sensitive droplet digital PCR method for detection of de novo EGFR T790M mutation in patients with Non-small cell lung cancer

Highly sensitive droplet digital PCR method for detection of de novo EGFR T790M mutation in patients with Non-small cell lung cancer

<p>Poor Prognosis With Coexistence Of <em>EGFR</em> T790M Mutation And Common <em>EGFR</em>-Activating Mutation In Non- Small Cell Lung Cancer</p>

The value of local consolidative therapy in Osimertinib-treated non-small cell lung cancer with oligo-residual disease

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