[Trastuzumab and blood-brain barrier]

Area of Science:

• Pharmacology
• Neuro-oncology
• Drug Delivery

Context:

• Trastuzumab, a large molecule antibody, faces significant challenges in penetrating the blood-brain barrier (BBB).
• Conditions like meningeal carcinomatosis and brain metastases can impair the BBB, yet still limit trastuzumab's CNS entry.
• Intravenous administration of trastuzumab results in suboptimal concentrations within the central nervous system (CNS).

Purpose:

• To evaluate the efficacy of trastuzumab in penetrating the central nervous system (CNS) for treating brain metastases.
• To assess the impact of whole-brain radiotherapy on trastuzumab's CNS penetration.
• To determine the therapeutic adequacy of trastuzumab levels in the CNS.

Summary:

• Trastuzumab's large size impedes its passage across the intact or compromised blood-brain barrier.
• While whole-brain radiotherapy can enhance penetration, achieved trastuzumab levels in the CNS are generally low and likely sub-therapeutic.
• These findings suggest limitations for intravenous trastuzumab in treating CNS manifestations of cancer.

Impact:

• Highlights the need for strategies to improve drug delivery across the BBB for CNS cancers.
• Suggests that trastuzumab alone may not be sufficient for treating brain metastases.
• Warrants further investigation into alternative therapies, such as lapatinib, for enhanced CNS efficacy.