Uncommon EGFR mutations associate with lower incidence of T790M mutation after EGFR-TKI treatment in patients with advanced NSCLC

Yang, Shuo; Mao, Shiqi; Li, Xuefei; Zhao, Chao; Liu, Qian; Yu, Xiaofei; Wang, Yan; Liu, Yiwei; Pan, Yingying; Wang, Chunyan; Gao, Guanghui; Li, Wei; Xiong, Anwen; Chen, Bin; Sun, Hui; He, Yayi; Wu, Fengying; Chen, Xiaoxia; Su, Chunxia; Ren, Shengxiang; Zhou, Caicun

doi:10.1016/j.lungcan.2019.11.018

Cited by 17 publications

(17 citation statements)

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“…In addition, osimertinib demonstrated moderate efficacy with an ORR of 50% and a median PFS of 8.2 months ( 62 ). Furthermore, some studies found that these patients had a significantly lower incidence of an acquired T790M mutation ( 63 ). Considering that patients with complex EGFR mutations and a secondary T790M mutation have a shorter PFS and OS when subsequently treated with osimertinib ( 64 ), first-line osimertinib is a choice for these patients.…”

Section: Common Concurrent Genetic Alterationsmentioning

confidence: 99%

Concurrent Genetic Alterations and Other Biomarkers Predict Treatment Efficacy of EGFR-TKIs in EGFR-Mutant Non-Small Cell Lung Cancer: A Review

et al. 2020

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Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) greatly improve the survival and quality of life of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, many patients exhibit de novo or primary/early resistance. In addition, patients who initially respond to EGFR-TKIs exhibit marked diversity in clinical outcomes. With the development of comprehensive genomic profiling, various mutations and concurrent (i.e., coexisting) genetic alterations have been discovered. Many studies have revealed that concurrent genetic alterations play an important role in the response and resistance of EGFR-mutant NSCLC to EGFR-TKIs. To optimize clinical outcomes, a better understanding of specific concurrent gene alterations and their impact on EGFR-TKI treatment efficacy is necessary. Further exploration of other biomarkers that can predict EGFR-TKI efficacy will help clinicians identify patients who may not respond to TKIs and allow them to choose appropriate treatment strategies. Here, we review the literature on specific gene alterations that coexist with EGFR mutations, including common alterations (intra-EGFR [on target] co-mutation, TP53, PIK3CA, and PTEN) and driver gene alterations (ALK, KRAS, ROS1, and MET). We also summarize data for other biomarkers (e.g., PD-L1 expression and BIM polymorphisms) associated with EGFR-TKI efficacy.

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Section: Common Concurrent Genetic Alterationsmentioning

confidence: 99%

Concurrent Genetic Alterations and Other Biomarkers Predict Treatment Efficacy of EGFR-TKIs in EGFR-Mutant Non-Small Cell Lung Cancer: A Review

et al. 2020

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“…Additionally, a multi-center phase II trial from Korea showed that the intracranial ORR of Osimertinib-treated patients harboring uncommon EGFR mutations was 40% (2/5) [ 15 ]. Nevertheless, the survival benefit was limited in the Korea study, with a median iTTP shorter than 9 months [ 32 ]. The iTTP of patients with uncommon mutations was also significantly shorter than that of patients with common mutations in our study.…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of advanced non-small cell lung cancer patients harboring distinct subtypes of EGFR mutations and receiving first-line tyrosine kinase inhibitors: brain metastasis and de novo T790M matters

et al. 2022

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Background The clinical features, survival outcomes and patterns of treatment failure of advanced non-small cell lung cancer (NSCLC) patients harboring distinct subtypes of EGFR mutations and receiving first-line EGFR tyrosine kinases inhibitor (TKIs) are not fully understood. Methods Consecutive metastatic EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs from October 2010 to March 2020 were enrolled and classified into two main groups based on the EGFR mutation subtypes: common mutation (L858R or exon 19 deletion), uncommon mutation (other EGFR mutations). Results Of the 1081 patients included, 74 (6.8%) harbored uncommon mutations. The baseline characteristics were generally balanced between the two groups, except that bone metastasis developed less frequently in patients with uncommon mutations (p = 0.02). No significant difference of survival outcomes was found between the two groups, except that among patients with baseline brain metastasis, the intracranial time to progression was significantly shorter in patients with uncommon mutations. Nine of the 17 patients with de novo T790M mutation received Osimertinib, whose overall survival tended to be longer than the remaining 8 patients without Osimertinib treatment (p = 0.08). The patterns of treatment failure were generally consistent between the two groups, except which patients with uncommon mutations had a higher risk developing progressive disease in the brain. Conclusion First-line EGFR-TKIs seemed to be less effective in controlling and preventing brain metastasis in patients with uncommon EGFR mutations and Osimertinib was associated with promising efficacy in patients with de novo T790M mutation, which warranted further validation.

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“…So far, this is the first time that Osimertinib was used to treat patient carrying EGFR19 insertion mutation. There are reports that the incidence of rare mutation T790M is low after treatment with afatinib[ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of EGFR-TKI sequential therapy in patients with EGFR exon 19 insertion-positive non-small-cell lung cancer: A case report

Shan¹,

Li²,

Zhao³

et al. 2022

WJCC

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BACKGROUND Insertions in exon 19 in the epidermal growth factor receptor gene (EGFR) is a rarely seen mutation in non-small cell lung cancer. These patients have been effectively treated with sequential EGFR tyrosine kinase inhibitors (TKIs). CASE SUMMARY Here, we presented a case of non-small cell lung cancer, stage IIIB, with EGFR exon 19 insertion mutation as detected in the right lower lobe by next-generation sequencing. The patient was sequentially treated with first, second, and third-generation EGFR TKIs after the surgical operation. The overall survival of the patient was 21.3 mo. There was no dynamic analysis of drug resistance mechanisms in targeted therapy. CONCLUSION This case emphasized the importance of following the guidelines. In patients with EGFR mutations, repeated and dynamic next-generation sequencing monitoring is necessary to prescribe a personalized treatment plan.

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Uncommon EGFR mutations associate with lower incidence of T790M mutation after EGFR-TKI treatment in patients with advanced NSCLC

Cited by 17 publications

References 50 publications

Concurrent Genetic Alterations and Other Biomarkers Predict Treatment Efficacy of EGFR-TKIs in EGFR-Mutant Non-Small Cell Lung Cancer: A Review

Concurrent Genetic Alterations and Other Biomarkers Predict Treatment Efficacy of EGFR-TKIs in EGFR-Mutant Non-Small Cell Lung Cancer: A Review

Clinical outcomes of advanced non-small cell lung cancer patients harboring distinct subtypes of EGFR mutations and receiving first-line tyrosine kinase inhibitors: brain metastasis and de novo T790M matters

Efficacy of EGFR-TKI sequential therapy in patients with EGFR exon 19 insertion-positive non-small-cell lung cancer: A case report

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