Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of central nervous system metastases from non-small cell lung cancer: the present and the future

Proto, Claudia; Imbimbo, Martina; Gallucci, Rosaria; Brissa, Angela; Signorelli, Diego; Vitali, Milena; Macerelli, Marianna; Corrao, Giulia; Ganzinelli, Monica; Greco, Francesca; Garassino, Marina Chiara; Russo, Giuseppe Lo

doi:10.21037/tlcr.2016.10.16

Cited by 32 publications

(23 citation statements)

References 130 publications

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“…The successful treatment of NSCLC with EGFR‐TKIs marks an era of targeted cancer therapy . Previous studies have proven that the prognosis of NSCLC patients with effective EGFR gene mutations can be significantly improved by EGFR‐TKI treatment .…”

Section: Discussionmentioning

confidence: 99%

“…The successful treatment of NSCLC with EGFR-TKIs marks an era of targeted cancer therapy. [12][13][14] Previous studies have proven that the prognosis of NSCLC patients with effective EGFR gene mutations can be significantly improved by EGFR-TKI treatment. [15][16][17] Studies have also shown that small molecule TKIs (gefitinib or erlotinib) are more effective in patients with mutations in exon 18-21 of the EGFR gene, especially those with mutations in exon 19, whereas these targeted drugs are almost ineffective in patients without mutations.…”

Section: Discussionmentioning

confidence: 99%

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Relationship between EGFR mutation and computed tomography characteristics of the lung in patients with lung adenocarcinoma

2018

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BackgroundThe aim of this study was to investigate the relationship between EGFR mutation and computed tomography (CT) features in patients with adenocarcinoma of the lung.MethodsOne hundred and ninety two lung adenocarcinoma patients who underwent surgery were retrospectively included in this study. Examination of EGFR gene mutation was performed on all resected tumor samples. The 192 recruited lung adenocarcinoma patients were divided into groups according to EGFR mutation status: patients with mutations in exons 18–21 (effective mutated, n = 61) and non‐mutated (n = 131). The clinical characteristics and lung CT imaging features of the two groups were recorded and compared. Univariate and logistic regression analysis were performed to identify the independent risk factors relevant to effective EGFR gene mutation.ResultsThe independent risk factors relevant to effective EGFR mutation were evaluated by logistic regression test. The results indicated that female gender (odds ratio [OR] 3.23), lung CT features of lymphangitis carcinomatosa (OR 2.66), semi‐solid lesion density (OR 3.56), and spicule sign (OR 1.61) were independent risk factors relevant to EGFR mutation.ConclusionFemale patients with lung CT features of lymphangitis carcinomatosa, semi‐solid lesion density, and spicule sign are more prone to harbor EGFR gene mutations and are more likely to benefit from targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Relationship between EGFR mutation and computed tomography characteristics of the lung in patients with lung adenocarcinoma

2018

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“…For advanced NSCLC patients with epidermal growth factor receptor (EGFR) activating mutations, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) including gefitinib, erlotinib, and afatinib are now considered to be standard first-line therapy based on evidence from several trials [3][4][5]. Although several researchers have demonstrated a certain activity of first-or second-generation EGFR-TKIs in EGFR-mutated NSCLC patients with CNS metastases [6], it was demonstrated that EGFR + NSCLC patients have a much higher risk of developing CNS metastases [7]. Treatment options for CNS metastases during or after first-or second-generation EGFR-TKIs include surgical resection, stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT) and chemotherapy, but with severe adverse effects or limited inability to cross the blood-brain barrier (BBB) [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Data from real world to evaluate the efficacy of osimertinib in non-small cell lung cancer patients with central nervous system metastasis

Xing

Hao

et al. 2019

Clin Transl Oncol

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Objectives Central nervous system (CNS) metastases are very common in patients with non-small-cell lung cancer (NSCLC). We aimed to explore the clinical impact of osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), on CNS metastases in patients with advanced NSCLC in real-world setting. Methods Patients with advanced NSCLC who received osimertinib after progression of early-generation EGFR-TKIs and CNS metastases on baseline brain scan were retrospectively collected. Primary outcomes were disease control rate (DCR) and progression-free survival (PFS), and secondary objectives were objective response rate (ORR), time to tumor response, median best percentage change from baseline in CNS target lesion (TL) size and safety.

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“…The efficacy of first-generation EGFR-TKIs against CNS metastatic lesions of EGFR-mutated NSCLC has been shown in several small phase 2 trials [3][4][5]. This is attributable to their ability to cross the blood-brain barrier (BBB) probably due to their low molecular weight [6]. However, their concentration in the cerebrospinal fluid is much lower than in the blood, which leads to frequent CNS failure after achieving systemic clinical benefit mainly due to pharmacokinetic limitations following acquisition of the T790M resistant mutation [7].…”

Section: Introductionmentioning

confidence: 99%

Complete Remission of Multiple Brain Metastases in a Patient with EGFR-Mutated Non-Small-Cell Lung Cancer Treated with First-Line Osimertinib without Radiotherapy

Ameku¹,

Higa

2020

Case Reports in Oncological Medicine

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Osimertinib has demonstrated efficacy against stable or asymptomatic central nervous system (CNS) metastases of epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) in phase 2 and 3 clinical trials that allowed prior CNS radiotherapy. However, the efficacy of osimertinib only or the optimal treatment combination or sequence of radiotherapy has not been investigated. A 74-year-old woman diagnosed with T4N1M1c Stage IVB lung adenocarcinoma with EGFR mutation presented with a left upper lobe mass and multiple bilateral lung metastases. A total of more than 20 asymptomatic multiple brain metastases with a maximum diameter of 12 mm were diagnosed simultaneously. Osimertinib was administered as first-line treatment. Whole brain radiotherapy was deferred because she had no neurological symptoms. After 5 weeks, the multiple brain metastases disappeared completely, together with the response in the lung lesions. This case demonstrated that first-line treatment with osimertinib could even achieve complete remission of multiple brain metastases comprising as many as twenty lesions of EGFR-mutated NSCLC without radiation therapy. Radiation therapy for brain metastases can be deferred or even withheld. A new treatment strategy for EGFR mutated NSCLC with CNS metastases should be investigated using osimertinib, especially regarding optimal combination or sequence of radiotherapy.

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Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of central nervous system metastases from non-small cell lung cancer: the present and the future

Cited by 32 publications

References 130 publications

Relationship between EGFR mutation and computed tomography characteristics of the lung in patients with lung adenocarcinoma

Relationship between EGFR mutation and computed tomography characteristics of the lung in patients with lung adenocarcinoma

Data from real world to evaluate the efficacy of osimertinib in non-small cell lung cancer patients with central nervous system metastasis

Complete Remission of Multiple Brain Metastases in a Patient with EGFR-Mutated Non-Small-Cell Lung Cancer Treated with First-Line Osimertinib without Radiotherapy

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