Penetrating the evidence of EGFR and ALK tyrosine kinase inhibitors for non-small cell lung cancer brain metastases

2018 ◽  
Vol 25 (3) ◽  
pp. 623-637
Author(s):  
Christan M Thomas ◽  
Chung-Shien Lee
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

The brain is a common metastatic site in lung cancer. Approximately one-third of patients will develop brain metastases during the course of their disease. Median overall survival has been reported between 3 and 14.8 months in patients with brain metastases compared to other metastatic sites. In addition, the lifetime incidence of brain metastases is increasing due to prolonged survival seen in non-small cell lung cancer (NSCLC) patients due to new systemic therapies and improved neuro-imaging techniques. Several targeted therapies—such as tyrosine kinase inhibitors targeting epidermal growth factor receptors and anaplastic lymphoma kinase—are active in NSCLC and have data to suggested possible effectiveness against brain metastases in these patients.

scholarly journals Management of Brain Metastases in Non–Small-Cell Lung Cancer

2019 ◽  
Vol 15 (11) ◽  
pp. 563-570 ◽  
Author(s):  
Vinicius Ernani ◽  
Thomas E. Stinchcombe
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
The United States ◽  
Small Cell ◽  
Small Cell Lung

Lung cancer is the leading cause of cancer-related death in the United States. Approximately 20% of these patients present with brain metastases (BMs). Surgical resection, stereotactic radiosurgery, and whole-brain radiation therapy have historically been the primary treatment modalities for patients with non–small-cell lung cancer (NSCLC) and BMs. The treatments for BMs have become complex with the discovery of targetable molecular drivers and the development of an astonishing number of tyrosine kinase inhibitors. Many of these tyrosine kinase inhibitors have robust and durable efficacy against CNS metastases. In many circumstances, these drugs can defer local therapy and even reduce the risk of CNS progression. More recently, immune checkpoint inhibitors have changed the treatment landscape for many patients with NSCLC; however, the role of immunotherapy in patients with BMs is the subject of ongoing investigations. This article will review the current data and our approach to patients with NSCLC and BMs.

scholarly journals Brain metastases in non-small-cell lung cancer: are tyrosine kinase inhibitors and checkpoint inhibitors now viable options?

2018 ◽  
Vol 25 ◽  
pp. 103 ◽  
Author(s):  
S. Morin-Ben Abdallah ◽  
A. Wong
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung

Significant progress has been made in the treatment of stage iv non-small-cell lung cancer (nsclc); however, the prognosis of patients with brain metastases remains poor. Resection and radiation therapy remain standard options. This issue is an important one because 10% of patients with nsclc have brain metastases at diagnosis, and 25%–40% develop brain metastases during their disease. Standard chemotherapy does not cross the blood–brain barrier. However, there is new hope that tyrosine kinase inhibitors (tkis) used in patients with identified targetable mutations such as mutations of EGFR and rearrangements of ALK could have activity in the central nervous system (cns). Furthermore, immunotherapy is increasingly becoming a standard option for patients with nsclc, and interest about the intracranial activity of those agents is growing. This review presents current data about the cns activity of the available major tkis and immunotherapy agents.

scholarly journals Tyrosine kinase inhibitors for EGFR- and ALK-mutated non-small cell lung cancer

ADMET & DMPK ◽  
2016 ◽  
Vol 4 (3) ◽  
pp. 186
Author(s):  
Jonathan R. Thompson ◽  
Smitha P. Menon ◽  
Grace K. Dy
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
The United States ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

<p class="ADMETkeywordsheading">Discovery of the epidermal growth receptor (EGFR) activating mutations and anaplastic lymphoma kinase (ALK) rearrangements has expanded the therapeutic landscape in non-small cell lung cancer (NSCLC). Survival outcomes for patients with these mutations have improved dramatically with EGFR and ALK tyrosine kinase inhibitors (TKIs). Multiple generations of EGFR and ALK TKIs have been rapidly developed, and patients and clinicians now have several options for first- and second-line treatments. While these small molecule TKIs have some similarities in therapeutic and pharmacologic profiles, the differences can be clinically substantial, allowing tailored treatment for each unique patient. This review details the clinical efficacy, pharmacology, safety profiles, CNS penetration, and mechanisms of resistance of the four EGFR TKIs and three ALK TKIs that are currently approved by the United States Food and Drug Administration (US FDA).</p>

scholarly journals Brain metastases in resected non-small cell lung cancer: The impact of different tyrosine kinase inhibitors

PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0215923
Author(s):  
Po-Jen Yun ◽  
Guan-Chyuan Wang ◽  
Ying-Yi Chen ◽  
Ti-Hui Wu ◽  
Hsu-Kai Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
The Impact
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