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Review
. 2024 May;41(5):1815-1842.
doi: 10.1007/s12325-024-02799-9. Epub 2024 Mar 21.

Clinical Management of Patients with Non-Small Cell Lung Cancer, Brain Metastases, and Actionable Genomic Alterations: A Systematic Literature Review

Mustafa Khasraw  1 , Priyanka Yalamanchili  2 , Anu Santhanagopal  2 , Chuntao Wu  2 , Maribel Salas  2   3 , Jie Meng  4 , Maha Karnoub  2 , Stephen Esker  2 , Enriqueta Felip  5
Affiliations
Review

Clinical Management of Patients with Non-Small Cell Lung Cancer, Brain Metastases, and Actionable Genomic Alterations: A Systematic Literature Review

Mustafa Khasraw et al. Adv Ther. 2024 May.

Abstract

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.

Keywords: EGFR mutation; Brain metastases; NSCLC; Systematic literature review.

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Conflict of interest statement

Mustafa Khasraw: Received grants or contracts from BioNTech, CNS Pharmaceuticals, Daiichi Sankyo, Inc., Immorna Therapeutics, Immvira Therapeutics, and Personalis, Inc.; received consulting fees from AnHeart Therapeutics, Berg Pharma, George Clinical, Manarini Stemline, and Servier; received honoraria from GSK; and participated on an advisory board for Berg Pharmaceuticals. Priyanka Yalamanchili, Chuntao Wu, Jie Meng are employees of Daiichi Sankyo, Inc. Maha Karnoub, Anu Santhanagopal, Maribel Salas, Stephen Esker are employees of Daiichi Sankyo, Inc. and are shareholders in the company. Enriqueta Felip: received consulting fees from AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Inc., Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point; received payment or honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann–La Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, Peervoice, Pfizer, Sanofi, Takeda, and Touch Oncology; and received support for attending meetings from AstraZeneca, Janssen, and Roche.

Figures

Fig. 1
Fig. 1
Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram of literature search results. Figure shows the flow of the study identification and selection process. In total, 7884 records were originally identified. After removal of duplicates, 3815 records were screened. Several records were excluded throughout the process for reasons such as the population being out of scope, not having results because of an ongoing study, or the study design being out of scope. Ultimately, 179 studies were included in this review
See this image and copyright information in PMC

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