The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

Cheng, Wood-Hi; Hsia, Te‐Chun; Tu, Chih‐Yen; Chen, Hung‐Jen

doi:10.2147/ott.s279540

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…Higher frequency of T790M acquisition in patients with exon 19 deletion, L858R, longer treatment duration of previous EGFR-TKIs, previous gefitinib treatment, initial liver metastasis, and rebiopsy at metastatic sites has been reported. The longer duration between the first and second rebiopsy among patients with the T790M mutation in the second biopsy has been found compared to those without T790M [50][51][52][53][54][55]. The presence of circulating EGFR cell-free DNA, including the exon 19 deletion, L858R mutation, or T790M mutation showed different influences on OS in patients with advanced EGFR-mutant pulmonary adenocarcinoma who have progressed on first-line EGFR-TKIs [55].…”

Section: Egfrmentioning

confidence: 91%

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

Luo

Liang²,

Huang³

et al. 2022

IJMS

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Lung cancers are life-threatening malignancies that cause great healthcare burdens in Taiwan and worldwide. The 5-year survival rate for Taiwanese patients with lung cancer is approximately 29%, an unsatisfactorily low number that remains to be improved. We first reviewed the molecular epidemiology derived from a deep proteogenomic resource in Taiwan. The nuclear factor erythroid 2-related factor 2 (NRF2)antioxidant mechanism was discovered to mediate the oncogenesis and tumor progression of lung adenocarcinoma. Additionally, DNA replication, glycolysis and stress response are positively associated with tumor stages, while cell-to-cell communication, signaling, integrin, G protein coupled receptors, ion channels and adaptive immunity are negatively associated with tumor stages. Three patient subgroups were discovered based on the clustering analysis of protein abundance in tumors. The first subgroup is associated with more advanced cancer stages and visceral pleural invasion, as well as higher mutation burdens. The second subgroup is associated with EGFR L858R mutations. The third subgroup is associated with PI3K/AKT pathways and cell cycles. Both EGFR and PI3K/AKT signaling pathways have been shown to induce NRF2 activation and tumor cell proliferation. We also reviewed the clinical evidence of patient outcomes in Taiwan given various approved targeted therapies, such as EGFR-tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK)inhibitors, in accordance with the patients’ characteristics. Somatic mutations occurred in EGFR, KRAS, HER2 and BRAF genes, and these mutations have been detected in 55.7%, 5.2%, 2.0% and 0.7% patients, respectively. The EGFR mutation is the most prevalent targetable mutation in Taiwan. EML4-ALK translocations have been found in 9.8% of patients with wild-type EGFR. The molecular profiling of advanced NSCLC is critical to optimal therapeutic decision-making. The patient characteristics, such as mutation profiles, protein expression profiles, drug-resistance profiles, molecular oncogenic mechanisms and patient subgroup systems together offer new strategies for personalized treatments and patient care.

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Section: Egfrmentioning

confidence: 91%

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

Luo

Liang²,

Huang³

et al. 2022

IJMS

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“…It is generally accepted that tissue biopsy serves as an inadequate gold standard or reference standard (48). The EGFR T790M mutation may be absent in certain cancer areas due to the heterogeneity of the cancer (49). Patients may have an advanced stage of NSCLC if their condition progresses throughout the course of the disease (50).…”

Section: Egfr Mutationsmentioning

confidence: 99%

Targeted Molecular Profiling of Non-small Cell Lung Cancer in India

Dhungel,

Mudagal,

Raj Sharma

et al. 2024

J Adv Immunopharmacol

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: Cancer often rates highly on lists of the world's most hazardous diseases and routinely appears high on lists of the illnesses that people fear the most. Due of its relevance to the subject at hand, this article concentrates on lung cancer rather than other forms of malignancy. Most patients, both those who have never smoked cigarette as well as those who have, are affected by NSCLC, the more common of these two types. The Mesenchymal – Epithelial Transition (MET) protein amplification, EGFR mutations, RET Fusions, and other possible therapeutic targets for the treatment of non-small cell lung cancer are highlighted in this article. The primary aim of this article is to provide a gist of the various mutations and targets' modes of action. It also covers the limits of the medicines that are currently being used to treat certain targets.

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“…Sequence osimertinib in the second‐line has shown promising results for treating progressive disease, mainly due to T790M resistance mutation 27 . However, our previous study showed that central nervous system (CNS) progression was inversely correlated with T790M mutation presence 28 . This may not only be due to the difficulties of biopsy of CNS lesions, but recognized mechanism of pharmacokinetic resistance, a poor CSF‐to‐plasma ratio of first‐ and second‐generation EGFR‐TKIs 29 …”

Section: Introductionmentioning

confidence: 98%

“…27 However, our previous study showed that central nervous system (CNS) progression was inversely correlated with T790M mutation presence. 28 This may not only be due to the difficulties of biopsy of CNS lesions, but recognized mechanism of pharmacokinetic resistance, a poor CSFto-plasma ratio of first-and second-generation EGFR-TKIs. 29 The identification of suitable candidates for treatment with local therapy or antiangiogenesis agents in combination with EGFR-TKIs and the sequencing strategy with osimertinib in CNS progression remains necessary.…”

Section: Introductionmentioning

confidence: 99%

The optimal therapy strategy for epidermal growth factor receptor‐mutated non‐small cell lung cancer patients with brain metastasis: A real‐world study from Taiwan

et al. 2022

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Background: The treatment options for epidermal growth factor receptor (EGFR)mutated non-small cell lung cancer (NSCLC) with brain metastases (BMs) include EGFR-tyrosine kinase inhibitors (TKIs), stereotactic radiosurgery (SRS), whole-brain radiotherapy, brain surgery, and antiangiogenesis therapy. As treatment options evolve, redefining optimal treatment strategies to improve survival are crucial. Methods: A total of 150 EGFR-mutant NSCLC patients with BMs who received firstor second-generation EGFR-TKIs as first-line treatment between January 2012 and October 2019 were included in this analysis. Results: After multivariate analysis, patients with the graded prognostic assessment for lung cancer using molecular markers (Lung-mol GPA) ≥3 (hazard ratio [HR]: 0.538, 95% confidence interval [CI]: 0.35-0.83), who received afatinib or erlotinib as first-line treatment (HR: 0.521, 95% CI: 0.33-0.82), underwent SRS therapy (HR: 0.531, 95% CI: 0.32-0.87), or were sequentially treated with osimertinib (HR: 0.400, 95% CI: 0.23-0.71) were associated with improved overall survival (OS). Furthermore, SRS plus EGFR-TKI provided more OS benefits in patients with Lung-mol GPA ≥3 compared with EGFR-TKI alone in our patient cohort (44.9 vs. 26.7 months, p = 0.005). The OS in patients who received sequential osimertinib therapy was significantly longer than those without osimertinib treatment (43.5 vs. 24.3 months, p < 0.001), regardless of T790 mutation status (positive vs. negative vs. unknown: 40.4 vs. 54.6 vs.43.4 months, p = 0.227). Conclusions:The study demonstrated that EGFR-mutant NSCLC patients with BMs could be precisely treated with SRS according to Lung-mol GPA ≥3. Sequential osimertinib was associated with prolonged survival, regardless of T790M status.K E Y W O R D S brain metastasis, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, graded prognostic assessment for lung cancer using molecular markers (lung-mol GPA), stereotactic radiosurgery

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The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

Cited by 6 publications

References 37 publications

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

Targeted Molecular Profiling of Non-small Cell Lung Cancer in India

The optimal therapy strategy for epidermal growth factor receptor‐mutated non‐small cell lung cancer patients with brain metastasis: A real‐world study from Taiwan

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