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Oral Targeted Therapies and Central Nervous System (CNS) Metastases

Michael P Gabay1, Scott M Wirth1, Joan M Stachnik1

  • 1Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.

CNS Drugs
|November 14, 2015
PubMed

Insights

This review summarizes oral targeted agents for brain metastases, including BRAF and EGFR inhibitors. It highlights the need for effective systemic therapies and documents intracranial activity, crucial for patients often excluded from clinical trials.

Area of Science:

  • Oncology
  • Pharmacology
  • Neurology

Background:

  • Brain metastases represent a significant challenge in cancer care, often lacking effective long-term systemic treatment options.
  • Intracranial activity data for many emerging targeted therapies is limited, hindering clinical decision-making.
  • Patients with brain metastases frequently face exclusion from clinical trials, further limiting research into systemic treatments.

Purpose of the Study:

  • To comprehensively review and summarize the clinical activity of various oral targeted agents specifically against brain metastases.
  • To consolidate pertinent data on intracranial efficacy for a range of targeted therapies, aiding clinicians in treatment selection.

Main Methods:

  • Systematic literature review of clinical studies evaluating oral targeted agents in patients with brain metastases.
  • Categorization of agents by their targeted pathways, including BRAF inhibitors, human epidermal growth factor receptor (EGFR) inhibitors, multi-kinase angiogenesis inhibitors, and ALK/c-MET/IGF-1 inhibitors.
  • Analysis of reported clinical activity, focusing on intracranial responses and overall survival benefits.

Main Results:

  • Summarized clinical activity data for specific oral targeted agents: BRAF inhibitors (dabrafenib, vemurafenib), EGFR inhibitors (lapatinib, gefitinib, erlotinib, afatinib), multi-kinase angiogenesis inhibitors (sorafenib, sunitinib, pazopanib, vandetanib), and ALK/c-MET/IGF-1 inhibitors (crizotinib, ceritinib).
  • Identified a critical need for more robust data on the intracranial efficacy of these agents.
  • Highlighted the therapeutic potential of certain oral targeted agents in managing brain metastases.

Conclusions:

  • Oral targeted agents show promise in treating brain metastases, but comprehensive data on their intracranial activity remains scarce.
  • This review provides essential summarized data for clinicians managing patients with brain metastases, addressing a gap in current research.
  • Further dedicated investigations into systemic therapies for brain metastases are crucial to improve patient outcomes.

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