Tyrosine Kinase Inhibitors Could Be Effective Against Non-small Cell Lung Cancer Brain Metastases Harboring Uncommon EGFR Mutations

Abstract

Background: The significance of uncommon epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC) and brain metastasis (BM) remains unclear. Cerebrospinal fluid (CSF) liquid biopsy is a novel tool for assessing EGFR mutations in BM. This study aimed to evaluate the EGFR mutations in patients with NSCLC and newly diagnosed BM and to examine the effect of EGFR tyrosine kinase inhibitors (TKI) on BM harboring CSF-tested uncommon EGFR mutations. Methods: This was a prospective study of 21 patients with NSCLC and BM diagnosed between 04/2018 and 01/2019. CSF was obtained to detect the BM EGFR mutations by next-generation sequencing. BM characteristics at magnetic resonance imaging (MRI) and EGFR-TKI response were examined. Results: Of 21 patients with NSCLC, 10 (47.6%) had leptomeningeal metastasis (LM), while 11 (52.4%) had brain parenchymal metastasis (BPM); 13 (61.9%) had confirmed EGFR mutation-positive primary tumors. The uncommon mutation rate in CSF ctDNA was 33.3% (7/21). Among those with EGFR mutation-positive primary tumors, the rate of uncommon EGFR mutations in CSF was 53.8% (7/13). Uncommon EGFR mutations were more common in patients with LM than in patients with PBM (6/11, 54.5% vs. 1/10, 10%), and included G719A, L861Q, L703P, and G575R. TKI was effective for four patients with BMs harboring uncommon EGFR mutations. Conclusion: In patients with NSCLC and LM, the rate of uncommon EGFR mutation was high. The BMs with uncommon EGFR mutations seem to respond to EGFR-TKI treatment. CSF liquid biopsy could reveal the EGFR genetic profile of the BM and help guide treatment using small-molecule TKI.

Effective Treatment With Afatinib of Lung Adenocarcinoma With Leptomeningeal Metastasis Harboring the Exon 18 p.G719A Mutation in the EGFR Gene Was Detected in Cerebrospinal Fluid: A Case Report

“…CSF liquid biopsy has emerged recently as a novel tool for assessing EGFR mutations in intracranial metastases. A recent study showed that in patients with NSCLC and leptomeningeal metastasis, the rate of uncommon EGFR mutation was high and that the brain metastases with uncommon EGFR mutations seem to respond to EGFR-TKI treatment (16). CSF liquid biopsy could reveal the EGFR genetic profile of the BM and help guide treatment using small-molecule TKI.…”

ctDNA-Based Liquid Biopsy of Cerebrospinal Fluid in Brain Cancer

“…The availability of targeted therapies highlights the importance of the identification of actionable genomic alterations or resistance mutations in genes, including EGFR , ALK , BRAF and HER2 , which have been detected from CSF ctDNA in several studies [ 20 , 21 , 31 , 32 , 94 , 95 , 96 ]. For example, EGFR–TKI resistance mutation EGFR T790M has been detected in the CSF ctDNA of lung cancer patients [ 94 , 97 ].…”

Таргетна Терапія Недрібноклітинного Раку Легені З Рідкісними Мутаціями Гена EGFR

“…Про аналогічний клінічний випадок успішного лікування пацієнта з лептоменінгеальними метастазами при НДРЛ осимертинібом 160 мг повідомлено для мутацій EGFR G719S та L861Q -через 1 міс лікування досягнута відповідь на терапію, а хворобу вдалося стабілізувати на час спостереження -1 рік [44]. Потенційна активність щодо метастазів у центральну нервову систему є особливо важливим фактором вибору ІТК для лікування рідкісних мутацій EGFR, оскільки нещодавнє, хоч і невелике, дослідження показало, що рідкісні мутації EGFR є відносно поширеними (54%) у метастазах у центральну нервову систему у пацієнтів із НДРЛ з мутаціями EGFR [45].…”