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Review
. 2024 Dec;26(12):1612-1638.
doi: 10.1007/s11912-024-01593-8. Epub 2024 Nov 8.

Immunotherapeutic and Targeted Strategies for Managing Brain Metastases from Common Cancer Origins: A State-of-the-Art Review

Vivek Podder  1 , Shreyas Bellur  1 , Kim Margolin  2 , Pooja Advani  3 , Reshma L Mahtani  1 , Vivek Subbiah  4 , Gabriella B Novo  1 , Tulika Ranjan  1 , Manmeet S Ahluwalia  5
Affiliations
Review

Immunotherapeutic and Targeted Strategies for Managing Brain Metastases from Common Cancer Origins: A State-of-the-Art Review

Vivek Podder et al. Curr Oncol Rep. 2024 Dec.

Abstract

Purpose of review: This review examines contemporary strategies for managing brain metastases (BM) from common cancers such as lung, breast, and melanoma. We evaluate the efficacy and applicability of targeted therapies and immunotherapies, exploring their potential to cross the blood-brain barrier and improve patient outcomes.

Recent findings: Recent studies have shown that tyrosine kinase inhibitors, immune checkpoint inhibitors, and ADCs effectively treat BM. These treatments can overcome the challenges posed by the blood-brain barrier and improve therapeutic outcomes. ADCs are promising because they can deliver cytotoxic agents directly to tumor cells, which reduces systemic toxicity and increases drug delivery efficiency to the brain. Personalized medicine is becoming increasingly significant in treatment decisions, with biomarkers playing an essential role. Advances in molecular genetics and drug development have led to more refined treatments, emphasizing the precision medicine framework. The management of BM is evolving, driven by drug efficacy, resistance mechanisms, and the need for personalized medicine. Integrating ADCs into treatment regimens represents a significant advancement in targeting metastatic brain tumors. Despite these advances, BM management still presents considerable challenges, requiring ongoing research and multi-institutional trials to optimize therapeutic strategies. This review outlines the current state and future directions in treating BM, highlighting the critical need for continued innovation and comprehensive clinical evaluations to improve survival rates and quality of life for affected patients.

Keywords: Antibody Drug Conjugates; Blood–Brain Barrier; Brain Metastases; Immunotherapy; Oncogenic Drivers; Targeted Therapy.

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Conflict of interest statement

Declarations. Conflict of Interests: VP, SB, and TR report no financial or non-financial conflicts of interest. KM reports being engaged as a consultant and global trial principal investigator for ImaginAb and as a consultant for Werewolf, Xilio, Beigene, Astra-Zeneca, and BMS. Additionally, KM has participated in mock ODAC roles for Beigene, Astra-Zeneca, Merck, and BMS. KM reports being engaged as a consultant and global trial principal investigator for ImaginAb. Additionally, KM 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. PA receives research funding for her institution from companies including Gilead, Agendia, Astra Zeneca, Caris Life Sciences, Seagen, Atossa Therapeutics, Modulation Therapeutics, Biovica International, Loxo Lilly, and Sermonix. PA serves on advisory boards for Epic Sciences, Biovica International, Astra Zeneca, and Hesian Labs, and provides consulting, honoraria, or speakers bureau services for GE Healthcare, AstraZeneca, MJH Lifesciences, Menarini Stemline, Iksuda Therapeutics, Breathe Biomedical, Daichi Sankyo, and Guardant Health. RLM reports the following: Consultant/Advisor: Agendia, Astra Zeneca, Daiichi, Eisai, Genentech, Gilead, Hologic, Lilly, Novartis, Pfizer, Puma, Sanofi, Sermonix, Stemline Research support: Gilead. VS reports grants from Eli Lilly/LOXO Oncology, Blueprint Medicines Corporation, Turning Point Therapeutics, Boston Pharmaceuticals, and Helsinn Pharmaceuticals. He also reports grants and services in an advisory board/consultant position for Eli Lilly/Loxo Oncology. He has received research grants from Roche/Genentech, Bayer, GlaxoSmithKline, Nanocarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth, Incyte, Fujifilm, D3, Pfizer, Multivir, Amgen, Abbvie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprint Medicines, Altum, Dragonfly Therapeutics, Takeda, National Comprehensive Cancer Network, NCI-CTEP, the University of Texas MD Anderson Cancer Center, Turning Point Therapeutics, Boston Pharmaceuticals, Novartis, Pharmamar, and Medimmune. He has served on an advisory board and as a consultant for Helsinn, Incyte, QED Pharma, Daiichi-Sankyo, Signant Health, Novartis, Relay Therapeutics, Roche, and Medimmune. He has received travel funds from Pharmamar, Incyte, ASCO, and ESMO, as well as other support from Medscape. MSA 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.

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