Coexistence of EGFR T790M mutation and common activating mutations in pretreatment non-small cell lung cancer: A systematic review and meta-analysis

Chen, Li-Yang; Molina-Vila, Miguel Ángel; Ruan, Sheng‐Yuan; Su, Kang-Yi; Liao, Wen-Chieh; Yu, Kai-Lun; Ho, Chao‐Chi; Shih, Jin‐Yuan; Yang, James Chih‐Hsin; Rosell, Rafael; Yang, Pan‐Chyr

doi:10.1016/j.lungcan.2016.01.019

Cited by 62 publications

(60 citation statements)

References 37 publications

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“…The T790M mutation can be detected in nearly 50% patients at time of acquiring TKIresistance (39). The results of a previous meta-analysis reported that pre-TKIs T790M is less frequent in patients harboring 19 del compared to those carrying the L858R mutation (14% vs. 22%; OR 0.59; P<0.001) (9). The trend of our study differed from the previous study in that T790M was more frequent in exon 19 deletion than in L858R among patients with acquired resistance to TKIs (53% vs. 36%; OR 1.87; P<0.001).…”

Section: Discussionmentioning

confidence: 98%

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The alteration of T790M between 19 del and L858R in NSCLC in the course of EGFR-TKIs therapy: a literature-based pooled analysis

et al. 2018

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Background: Treatment-naive epidermal growth factor receptor (EGFR) T790M mutation is more inclined to coexist with L858R than with 19 del in non-small cell lung cancer (NSCLC) patients. However, EGFRtyrosine kinase inhibitors (EGFR-TKIs) might alter this status. We sought to compare the prevalence of T790M upon acquired resistance to EGFR-TKIs between 19 del and L858R by assembling all existing data.Methods: Electronic databases were comprehensively searched for eligible studies. The primary endpoint was the odds ratio (OR) of T790M mutation in NSCLC co-existing with L858R mutation and 19 del upon resistance to first-generation EGFR-TKIs. A random effects model was used. Stratified analysis was performed based on study type (retrospective and prospective), race (Asians and Caucasians) and sample type (tissue and plasma). Results: A total of 25 studies involving 1,770 patients were included. The overall T790M existent rate was 45.25%. Post-resistance T790M was more frequent in 19 del than in L858R mutated patients (53% vs. 36%; OR 1.87; P<0.001). All outcomes of subgroup and overall analyses were similar. In contrast, we re-analyzed the previous meta-analysis, finding that the pooled rate of pretreatment T790M was 14% and 22% in 19 del and L858R respectively (OR 0.59; P<0.001). The increase of T790M rate was 2.79-fold in 19 del and only 0.63-fold in L858R in the course of EGFR-TKIs therapy.Conclusions: Opposite to the situation of de novo T790M, it was observed that T790M was more frequent in exon 19 deletion than in L858R among patients with acquired resistance to EGFR-TKIs. The difference in T790M alteration between 19 del and L858R encourages development of detection or treatment strategies for the specific resistance mechanism.

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Section: Discussionmentioning

confidence: 98%

“…Patients with co-existing L858R and 19 del mutations were excluded. Original data from previous meta-analysis were also extracted and re-analyzed to explore the mechanism of drug resistance during TKI therapy (9). We performed subgroup analyses according to the study design, population race, and sample types.…”

Section: Data Extraction and Quality Assessmentmentioning

confidence: 99%

The alteration of T790M between 19 del and L858R in NSCLC in the course of EGFR-TKIs therapy: a literature-based pooled analysis

et al. 2018

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“…These cases were reported by various methods on both tissue and plasma with detection rate ranging from 0.32% to 78.95%. [30] When initially present, T790M clone is likely to overgrow after the driver mutation responds to TKI treatment. Many studies have reported a poorer survival in this category of patients.…”

Section: Discussionmentioning

confidence: 99%

The detection of primary and secondary EGFR mutations using droplet digital PCR in patients with nonsmall cell lung cancer

et al. 2018

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Background:We share our experience of using droplet digital polymerase chain reaction (DdPCR) in liquid biopsy specimens for detecting primary and secondary epidermal growth factor receptor (EGFR) mutations among patients with nonsmall-cell lung cancer who had tissue biopsy initially analyzed for del19, L858R and T790M.Materials and Methods:Three groups of patients were chosen: Group 1: patients positive for EGFR mutation (del 19 or L858R) by conventional tissue biopsy that were treatment naïve, Group 2: patients positive for EGFR mutation (del 19 or L858R) by conventional tissue biopsy with acquired resistance to tyrosine kinase inhibitor (TKI) therapy, documented by radiology, and Group 3: no known EGFR mutation detected on primary tissue biopsy and treatment naive.Results:One hundred and thirty-three patients were included in the study. Group 1 had 40 cases, of which 21 (52.5%) and 19 (47.5%) were positive for del19 and L858R mutations, respectively, by tissue biopsy. DdPCR detected primary mutation in all but 5 cases. DdPCR additionally found four patients to have T790M mutation. Group 2 had 73 cases and DdPCR detected T790M mutation in 39 (53.4%) cases. Liquid biopsy also picked the original primary mutation in 56/73 cases. Secondary tissue biopsy for T790M mutation status was performed in 11 patients and while it detected mutation in 2 out of 11 cases, DdPCR detected the same in 7 cases, thus providing significantly superior yield (46% difference, McNemar's test, P value 0.063). Tissue biopsy additionally detected c-MET amplification in a patient who had T790M mutation on liquid biopsy. Group 3 had 20 patients and none were falsely positive for EGFR mutation on liquid biopsy. Overall, DdPCR had a Cohen's kappa of 0.82 (standard error 0.074, 95% CI 0.68–0.97) indicating “very good agreement” with conventional tissue biopsy.Conclusion:DdPCR demonstrated 87.5% sensitivity and 100% specificity in detecting primary EGFR mutations in patients who were treatment naïve with overall positive and negative predictive value of 100% and 80%, respectively. DdPCR demonstrated T790M mutation postprogression on TKI therapy in 53.4% patients.

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“…This mutation is reported in 50-60% of cases with acquired resistance to EGFR-TKIs (7,9). The mutation detected rates are different from the mutation detection methods (11). T790M substitution has been shown to alter the proper binding of the drug to the ATP pocket of EGFR and/or return the affinity of the ATP to the drug to the wild-type level (8,9).…”

Section: Introductionmentioning

confidence: 99%

The detectability of the pretreatment EGFR T790M mutations in lung adenocarcinoma using CAST-PCR and digital PCR

Tatematsu¹,

Okuda²,

Suzuki³

et al. 2017

J. Thorac. Dis.

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Background: A gatekeeper T790M mutation is thought to cause resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. The detection of a 2nd mutation is important for planning the next therapy when patients acquire resistance to the first line EGFR-TKI. Conclusions: Our study shows that the pretreatment incidence of T790M mutation was less than that reported in previous studies. In order to clinically use pretreatment EGFR T790M mutation identification method, we should clarify the adequate methods and tissue preserved status.

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Coexistence of EGFR T790M mutation and common activating mutations in pretreatment non-small cell lung cancer: A systematic review and meta-analysis

Cited by 62 publications

References 37 publications

The alteration of T790M between 19 del and L858R in NSCLC in the course of EGFR-TKIs therapy: a literature-based pooled analysis

The alteration of T790M between 19 del and L858R in NSCLC in the course of EGFR-TKIs therapy: a literature-based pooled analysis

The detection of primary and secondary EGFR mutations using droplet digital PCR in patients with nonsmall cell lung cancer

The detectability of the pretreatment EGFR T790M mutations in lung adenocarcinoma using CAST-PCR and digital PCR

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