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Clinical Management of Patients with Non-Small Cell Lung Cancer, Brain Metastases, and Actionable Genomic
Mustafa Khasraw1, Priyanka Yalamanchili2, Anu Santhanagopal2
1The Duke Cancer Institute, School of Medicine, Duke University, 20 Duke Medicine Cir, Durham, NC, 27710, USA. mustafa.khasraw@duke.edu.
Introduction:
Nearly 60% of patients with non-small cell lung cancer (NSCLC) present with metastatic disease, and approximately 20% have brain metastases (BrMs) at diagnosis. During the disease course, 25-50% of patients will develop BrMs. Despite available treatments, survival rates for patients with NSCLC and BrMs remain low, and their overall prognosis is poor. Even with newer agents for NSCLC, options for treating BrMs can be limited by their ineffective transport across the blood-brain barrier (BBB) and the unique brain tumor microenvironment. The presence of actionable genomic alterations (AGAs) is a key determinant of optimal treatment selection, which aims to maximize responses and minimize toxicities. The objective of this systematic literature review (SLR) was to understand the current landscape of the clinical management of patients with NSCLC and BrMs, particularly those with AGAs.
Method:
A Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-compliant SLR was conducted to identify studies in patients with BrMs in NSCLC. Searches used the EMBASE and MEDLINE® databases, and articles published between January 1, 2017 and September 26, 2022 were reviewed.
Results:
Overall, 179 studies were included in the SLR. This subset review focused on 80 studies that included patients with NSCLC, BrMs, and AGAs (19 randomized controlled trials [RCTs], two single-arm studies, and 59 observational studies). Sixty-four of the 80 studies reported on epidermal growth factor receptor (EGFR) mutations, 14 on anaplastic lymphoma kinase (ALK) alterations, and two on both alterations. Ninety-five percent of studies evaluated targeted therapy. All RCTs allowed patients with previously treated, asymptomatic, or neurologically stable BrMs; the percentage of asymptomatic BrMs varied across observational studies.
Conclusions:
Although targeted therapies demonstrate systemic benefits for patients with NSCLC, BrMs, and AGAs, there remains a continued need for effective therapies to treat and prevent BrMs in this population. Increased BBB permeability of emerging therapies may improve outcomes for this population.
Insights
Targeted therapies show promise for non-small cell lung cancer (NSCLC) with brain metastases (BrMs) and actionable genomic alterations (AGAs). However, improved treatments are still needed to effectively manage and prevent BrMs in this patient group.
Area of Science:
- Oncology
- Neurology
- Genomics
Background:
- Metastatic non-small cell lung cancer (NSCLC) frequently involves brain metastases (BrMs), with poor prognoses despite current treatments.
- Blood-brain barrier (BBB) penetration and the brain tumor microenvironment limit treatment efficacy for BrMs.
- Actionable genomic alterations (AGAs) are crucial for guiding optimal treatment selection in NSCLC.
Purpose of the Study:
- To systematically review the clinical management landscape of NSCLC patients with BrMs, with a focus on those harboring AGAs.
Main Methods:
- A systematic literature review (SLR) adhering to PRISMA guidelines was performed.
- Searches were conducted in EMBASE and MEDLINE databases for studies published between January 1, 2017, and September 26, 2022.
- Eighty studies focusing on NSCLC, BrMs, and AGAs were included in the subset analysis.
Main Results:
- The review included 179 studies, with 80 specifically analyzing NSCLC, BrMs, and AGAs.
- Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) alterations were the most frequently reported AGAs.
- Targeted therapies were evaluated in 95% of the studies, with randomized controlled trials (RCTs) typically including patients with treated, asymptomatic, or neurologically stable BrMs.
Conclusions:
- Targeted therapies offer systemic benefits for NSCLC patients with BrMs and AGAs.
- There is an ongoing need for novel therapies to treat and prevent BrMs in this population.
- Enhancing the ability of emerging therapies to cross the BBB may lead to improved patient outcomes.
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