Emerging and investigational targeted chemotherapy and immunotherapy agents for metastatic brain tumors

ABSTRACT

Introduction

Metastases to the central nervous system are the most common cause of malignant intracranial tumors in adults. Current standard of care includes surgery and radiation, but overall survival remains poor. A range of systemic therapies are emerging as promising treatment options for these patients.

Areas covered

This study reviews novel drug regimens that are under investigation in phase 1 and 2 clinical trials. To identify relevant therapies under clinical investigation, a search was performed on http://clinicaltrials.gov and Pubmed with the keywords brain metastasis, Phase I clinical trial, and Phase II clinical trial from 2016 to 2020. The authors detail the mechanisms of action of all trial agents, outline evidence for their utility, and summarize the current state of the field.

Expert opinion

Current advancements in the medical management of brain metastases can be categorized into targeted therapies, methods of overcoming treatment resistance, novel combinations of therapies, and modulation of the tumor microenvironment with a specific focus on immunotherapy. Each of these realms holds great promise for the field going forward. A more streamlined structure for enrollment into clinical trials will be a crucial step in accelerating progress in this area.

KEYWORDS:

• Brain metastasis
• lung cancer
• melanoma
• breast cancer
• renal cell carcinoma
• clinical trials
• immunotherapy
• tyrosine kinase inhibitors
• small molecule inhibitors
• early phase trial

Article highlights

• Overall survival among patients with intracranial metastatic disease remains poor despite standard surgery and radiation, highlighting a need for advancement in the realm of systemic therapies

• Targeted therapies, those that have specificity for key receptors or intracellular pathways involved in tumorigenesis, afford high anti-tumor activity with more limited side-effects than cytotoxic agents

• Tumor resistance to current standard therapies poses a substantial barrier to cure, but a variety of agents are under investigation that have the ability to overcome resistance-causing mutations

• Immunotherapeutic agents, such as checkpoint inhibitors, will likely play a growing role in this patient population as our understanding of the tumor microenvironment grows

• Overall enrollment in clinical trials of patients with CNS tumors remains low and presents one of the most notable barriers to progress in this field

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.