The role of systemic and targeted therapies in brain metastases

Abstract

For many years, brain metastases (BMs) have been considered as the final stage of a disease course and engendered skepticism about the efficacy of treatments. Local treatments, mainly, whole-brain radiotherapy have been the standard of care, whereas chemotherapy has been considered of limited efficacy due to the potential role of blood–brain barrier.

Keywords::

• BRAF V600E melanoma
• brain metastases
• EGFR mutations
• HER2 breast cancer
• target therapy

Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Brain metastases (BMs) represent a major issue in clinical practice, since symptoms incur an important impairment of quality of life and can cause a rapid decline in patients’ survival.

• Systemic treatments, especially chemotherapy, have showed limited efficacy to control intracranial disease and improve clinical conditions and survival.

• The incidence of BMs in breast cancer patients have increased over the past decade, probably due to the prolongation in survival obtained with current treatments.

• HER2 overexpression is a risk factor for BMs in breast cancer patients.

• The combination of capecitabine and lapatinib demonstrated a certain efficacy against BMs from HER2-positive breast cancer.

• Most of the chemotherapeutic agents are unable to penetrate the blood–brain barrier. EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs), given their low molecular weight, may be able to reach a higher concentration in brain tissues.

• Various reports and small studies demonstrated the efficacy of EGFR TKIs in obtaining dramatic responses in BMs. The highest response rate on BMs was obtained in patients harboring EGFR mutations.

• Efficacy of vemurafenib and dabrafenib on BMs from melanoma has been reported.

• Efforts should be made to perform prospective trials on selected populations using clinical factors or genetic alterations in which targeted agents are used concomitantly with, or instead of, WBRT, with the aim of improving both the survival outcomes and the quality of life of the patients.