Faculty, Staff and Student Publications
Publication Date
10-1-2023
Journal
Nature Reviews Clinical Oncology
Abstract
The improved survival outcomes of patients with non-small-cell lung cancer (NSCLC), largely owing to the improved control of systemic disease provided by immune-checkpoint inhibitors and novel targeted therapies, have highlighted the challenges posed by central nervous system (CNS) metastases as a devastating yet common complication, with up to 50% of patients developing such lesions during the course of the disease. Early-generation tyrosine-kinase inhibitors (TKIs) often provide robust systemic disease control in patients with oncogene-driven NSCLCs, although these agents are usually unable to accumulate to therapeutically relevant concentrations in the CNS owing to an inability to cross the blood-brain barrier. However, the past few years have seen a paradigm shift with the emergence of several novel or later-generation TKIs with improved CNS penetrance. Such agents have promising levels of activity against brain metastases, as demonstrated by data from preclinical and clinical studies. In this Review, we describe current preclinical and clinical evidence of the intracranial activity of TKIs targeting various oncogenic drivers in patients with NSCLC, with a focus on newer agents with enhanced CNS penetration, leptomeningeal disease and the need for intrathecal treatment options. We also discuss evolving assessment criteria and regulatory considerations for future clinical investigations.
Keywords
Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Oncogenes, Patients, Blood-Brain Barrier
DOI
10.1038/s41571-023-00808-4
PMID
37592034
PMCID
PMC10851171
PubMedCentral® Posted Date
10-1-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
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