Clinical outcome according to the level of preexisting epidermal growth factor receptor T790M mutation in patients with lung cancer harboring sensitive epidermal growth factor receptor mutations

Lee, Young‐Joo; Lee, Geon Kook; Lee, Yeon Su; Zhang, Wenji; Hwang, Jaehoon; Nam, Byung Ho; Kim, Seok Hyun; Kim, Joo Hang; Yun, Tak; Han, Ji Youn; Kim, Heung Tae; Lee, Jin Soo

doi:10.1002/cncr.28711

Cited by 58 publications

(58 citation statements)

References 25 publications

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“…In patients with lung cancer, it has been well documented that T790M mutations, although the minority at the time of diagnosis, become predominant after resistance to EGFR inhibitors. 22 In breast cancer, a similar phenomenon is being observed with ESR1. ESR1 is the gene that encodes for ER.…”

Section: Key Pointssupporting

confidence: 56%

Precision Medicine for Metastatic Breast Cancer

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2015

American Society of Clinical Oncology Educational Book

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OVERVIEWGenomic studies have shown that large numbers of candidate targets are observed in breast cancer. Nevertheless, only a few of them are validated as relevant targets in clinical studies. Estrogen receptor (ER) and HER2 expressions could be associated with a level I evidence. Beyond ER and HER2, BRCA and PIK3CA mutations (when targeted with alpha-specific PI3K inhibitors) could be considered as promising targets in breast cancer since they have been associated with objective responses in phase I/II trials. In addition to these four molecular alterations, several others have shown promising results in preclinical studies and are being investigated in clinical trials. These genomic alterations include AKT1, ERBB2, and ESR1 mutations. These considerations highlight the lack of evidence for using multiplex technologies to individualize therapy in metastatic breast cancer. Sequencing multiple genes to treat metastatic breast cancer is very promising but should be done in the context of clinical trials, either to enrich phase I/II trials in patients with genomic alterations or to show medical usefulness of new biotechnologies like next-generation sequencing (NGS). Although most current approaches of precision medicine are aiming at targeting drivers, additional applications could be developed in the future. This includes the identification of DNA repair deficiencies, mechanisms of immune suppression, and identification of minority lethal subclones. Finally, one of the very promising applications of genomics for metastatic breast cancer is the identification of pathway activation or defects at the individual level. For example, gene expression and single nucleotide polymorphisms (SNP) signatures are being developed to detect kinase (such as mammalian target of rapamycin [mTOR]/CDK4) activations or DNA repair deficiencies.

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Section: Key Pointssupporting

confidence: 56%

Precision Medicine for Metastatic Breast Cancer

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Onesti

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2015

American Society of Clinical Oncology Educational Book

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“…Oxnard et al (25) and Hata et al (28) reported that patients who acquired TKI resistance and harboured the T790M mutation experienced a significantly longer post-progression survival time than patients without the T790M mutation (19 vs. 12 months; P=0.036). However, Lee et al (29) reported that the patients with T790M-positive tumours experienced a shorter overall survival time than those with T790M-negative tumours (median, 9.1 vs. 18.7 months; P=0.018). Numerous factors affect the OS, including the patient's performance status score, cancer therapy, disease stage, and importantly, organ metastasis.…”

Section: Discussionmentioning

confidence: 98%

A sensitive and practical method to detect the T790M mutation in the epidermal growth factor receptor

et al. 2016

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Abstract. The current study aimed to develop a method to rapidly, sensitively and practically screen for the epidermal growth factor receptor (EGFR) T790M mutation. This method combines an allele-specific competitive blocker (ACB) with a TaqMan quantitative polymerase chain reaction (PCR) amplification refractory mutation system (ARMS) in a one-step reaction. Using a mimic of a human genomic DNA panel containing serially diluted mutant alleles, the performance efficacy of this method was assessed. Using this method, the EGFR T790M mutation was detected in tyrosine kinase inhibitor (TKI)-naïve samples obtained from 27 non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. The association between de novo T790M mutations and the clinical benefit of EGFR-TKI treatment was also analysed. The sensitivity of this method was as low as 0.01%. In the samples from the 27 NSCLC patients, this method identified 6 mutant patients (22.2%), which was higher than the detection rate with scorpion ARMS (0.0%). No clinical variables were associated with the occurrence of a de novo T790M mutation. The median progression-free survival time in the TKI-naïve patients with a T790M mutation was shorter that that of patients without the mutation, but the difference was not significant (3.2 vs. 19.5 months, respectively; P=0.256). The median overall survival time in the groups with or without T790M mutation also did not significantly differ (10 vs. 20 months, respectively; P=0.689). Overall, the ACB-ARMS PCR method could be useful for detecting the EGFR T790M mutation in clinical samples that contain only a small number of mutant alleles. The clinical significance of a de novo T790M mutation should be further investigated.

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“…Several investigators applied highly sensitive assays to evaluate whether the presence of T790M subclones in treatment-naïve tumors is associated with shorter duration of response to first-generation TKIs [26,30,31,32,34]. The majority of studies showed a tendency to shorter PFS in patients with this mutation [30,31,32,34,44,45].…”

Section: Discussionmentioning

confidence: 99%

“…The majority of studies showed a tendency to shorter PFS in patients with this mutation [30,31,32,34,44,45]. In support of a biological role of mosaic T790M mutations, Costa et al [32] and Rosell et al [46] observed that low-abundance T790M alleles are characteristic only for lung cancer with EGFR TKI-sensitizing mutations but are uncommon for EGFR wt and KRAS-mutated tumors (see online supplemental materials for these articles).…”

Section: Discussionmentioning

confidence: 99%

“…Most importantly, multiple studies utilizing highly sensitive techniques revealed that EGFR T790M is often mosaically present in NSCLC before treatment, although the proportion of T790M-mutated cells is low [26,27,28,29]. Furthermore, some investigations demonstrated a correlation between the presence of T790M subclones in chemo-naïve NSCLC samples and the time to TKI treatment failure [13,30,31,32,33,34]. However, other reports suggest that the detection of residual amounts of EGFR T790M allele is largely related to the methodological artifacts than to genuine genetic heterogeneity of NSCLC cells [35].…”

Section: Introductionmentioning

confidence: 99%

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EGFR T790M Mutation in TKI-Naïve Clinical Samples: Frequency, Tissue Mosaicism, Predictive Value and Awareness on Artifacts

et al. 2018

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Background: This study evaluated the distribution of epidermal growth factor receptor (EGFR) T790M mutations in treatment-naïve tumor and normal samples obtained from cancer patients. Methods: We utilized allele-specific PCR (AS-PCR), digital droplet PCR (ddPCR) and next generation sequencing (NGS) to detect EGFR T790M allele in several collections of tumor and normal human tissues. Results: AS-PCR analysis of treatment-naïve tumor samples revealed somatic T790M mutation in 3/394 (1%) non-small cell lung carcinomas (NSCLC) carrying the tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutation, but in none of 334 NSCLC lacking EGFR exon 19 deletions (ex19del) or L858R substitutions and in none of 235 non-lung tumors. Use of highly sensitive and quantitative assays, such as ddPCR and NGS, produced a high number of T790M-specific signals even in presumably T790M-negative DNA specimens. This background noise was evidently higher in degraded DNA isolated from formalin-fixed paraffin-embedded tissues as compared to high molecular weight DNA. A combination of AS-PCR, ddPCR and NGS revealed mosaic EGFR T790M allele in 2/68 (3%) NSCLC treated with the first-generation TKI. Both these tumors produced evident and durable response to gefitinib. Conclusion: Detection of mosaic EGFR T790M mutation in treatment-naïve samples may be compromised by yet unresolved technical issues and may have limited clinical value.

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Clinical outcome according to the level of preexisting epidermal growth factor receptor T790M mutation in patients with lung cancer harboring sensitive epidermal growth factor receptor mutations

Cited by 58 publications

References 25 publications

Precision Medicine for Metastatic Breast Cancer

Precision Medicine for Metastatic Breast Cancer

A sensitive and practical method to detect the T790M mutation in the epidermal growth factor receptor

EGFR T790M Mutation in TKI-Naïve Clinical Samples: Frequency, Tissue Mosaicism, Predictive Value and Awareness on Artifacts

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