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Review
. 2024 Oct 3;16(19):3388.
doi: 10.3390/cancers16193388.

Immune Checkpoint Inhibitors in the Management of Brain Metastases from Non-Small Cell Lung Cancer: A Comprehensive Review of Current Trials, Guidelines and Future Directions

Tulika Ranjan  1 , Vivek Podder  1 , Kim Margolin  2 , Vamsidhar Velcheti  3 , Arun Maharaj  1 , Manmeet Singh Ahluwalia  1
Affiliations
Review

Immune Checkpoint Inhibitors in the Management of Brain Metastases from Non-Small Cell Lung Cancer: A Comprehensive Review of Current Trials, Guidelines and Future Directions

Tulika Ranjan et al. Cancers (Basel). .

Abstract

Background: Brain metastases (BM) are a common, severe complication in patients with non-small cell lung cancer (NSCLC) and are difficult to treat due to their complex tumor biology and the intricate microenvironment of the brain.

Objectives: This review examines the current role of immune checkpoint inhibitors (ICIs) in treating NSCLC with BM, focusing on the latest clinical trials, emerging strategies, current guidelines, and future directions. We highlight the efficacy of ICIs as monotherapy and in combination with other treatments such as radiotherapy, stereotactic radiosurgery, chemotherapy, and anti-VEGF agents.

Results: While no single treatment sequence is universally accepted, combining ICIs with traditional therapies forms the core of the current treatment protocols. ICIs targeting the PD-1/PD-L1 pathway have significantly advanced NSCLC treatment, demonstrated by improved overall and progression-free survival in various settings. However, optimizing these benefits requires careful consideration of potential side effects, including cognitive decline and radiation necrosis, and the impact of steroid use on ICI efficacy.

Conclusion: The review underscores the necessity for a personalized, integrated multidisciplinary treatment approach. Future research should focus on refining combination therapies and understanding the optimal sequence and timing of treatment.

Keywords: brain metastasis; combination therapy; immune checkpoint inhibitors; non-small cell lung cancer; radiotherapy.

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Conflict of interest statement

T.R., V.P. and A.M. report no financial or non-financial conflicts of interest. K.M. reports being engaged as a consultant and global trial principal investigator for ImaginAb. Additionally, K.M. has participated in mock ODAC roles for Beigene, Astra-Zeneca, Merck, Daiichi-Sankyo, and BMS. KM is part of the adjuvant trial steering committee and local trial principal investigator for Regeneron and holds local trial principal investigator roles for Agenus and ImmunoCore. Velcheti reports honoraria from ITeos Therapeutics; serving in an advisory and/or consultant role for Bristol Myers Squibb, Merck, AstraZeneca/MedImmune, GlaxoSmithKline, Amgen, Elevation Oncology, Merus, Jansen oncology, Taiho Oncology; and research funding to his institution from Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantWorks, Genoptix, Altor BioScience, Merck, Bristol Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline. M.S.A. has received grants from Seagen and holds consulting roles with several companies, including Bayer, Kiyatec, Insightec, GSK, Xoft, Nuvation, SDP Oncology, Apollomics, Prelude, Janssen, Voyager Therapeutics, Viewray, Caris Lifesciences, Pyramid Biosciences, Varian Medical Systems, Cairn Therapeutics, Anheart Therapeutics, Theraguix, Menarini Ricerche, Sumitomo Pharma Oncology, Autem Therapeutics, GT Medical Technologies, Allovir, and Equillium Bio. He is on the Data Safety Monitoring Committee for VBI Vaccines and serves on the Scientific Advisory Board for Modifi Biosciences and Bugworks. Additionally, MSA is a shareholder in Mimivax, Cytodyn, MedInnovate Advisors LLC, and Trisalus Lifesciences.

Figures

Figure 1
Figure 1
Mechanisms of Action of Immune Checkpoint Inhibitors on Tumor Cells. Created with BioRender.com.
See this image and copyright information in PMC

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