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ACTIVITY OF TRASTUZUMAB-EMTANSINE (TDM1) IN HER2-POSITIVE BREAST CANCER BRAIN METASTASES: A CASE SERIES
Kevin C Keith1, Yueh Lee2, Matthew G Ewend3
1College of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425.
Abstract:
The incidence of breast cancer brain metastasis (BCBM) is increasing due in part to improved management of systemic disease and prolonged survival. Despite this growing population of patients, there exists little consensus for the treatment of HER2-positive BCBM. Lapatinib, the only brain permeable targeted agent for HER2-positive cancer, has demonstrated limited intracranial response rates and little improvement in progression free survival (PFS) for HER-2 positive patients. Size constraints are believed to prevent larger monoclonal antibodies, such as pertuzumab and trastuzumab, from crossing the blood brain barrier (BBB). However, emerging evidence reveals that the BBB is perturbed in the setting of metastases, allowing for improved penetrance of these larger targeted agents. The disrupted BBB may allow for passage of ado-trastuzumab emtansine (TDM1), though little clinical information about its activity in BCBM patients is currently known.
Insights
The study explores treatments for HER2-positive breast cancer brain metastases (BCBM). Emerging evidence suggests larger targeted agents may cross the blood-brain barrier, offering new therapeutic possibilities for BCBM patients.
Area of Science:
- Oncology
- Neurology
- Pharmacology
Background:
- Breast cancer brain metastasis (BCBM) incidence is rising with improved systemic treatment and survival.
- Limited consensus exists for treating HER2-positive BCBM.
- Current brain-penetrant agents like lapatinib show limited efficacy.
Purpose of the Study:
- To evaluate the potential of larger targeted agents for HER2-positive BCBM.
- To explore the impact of a perturbed blood-brain barrier (BBB) on drug penetrance.
- To assess the unknown clinical activity of ado-trastuzumab emtansine (TDM1) in BCBM.
Main Methods:
- Review of emerging evidence on BBB permeability in brain metastases.
- Analysis of drug characteristics, including size and brain penetrance.
- Exploration of clinical data regarding TDM1 activity in BCBM.
Main Results:
- Lapatinib demonstrates limited intracranial response and progression-free survival (PFS) in HER2-positive BCBM.
- Monoclonal antibodies (e.g., pertuzumab, trastuzumab) face size constraints for BBB crossing.
- Perturbed BBB in metastases may permit passage of larger agents, including TDM1.
Conclusions:
- The disrupted BBB in BCBM may enable enhanced penetrance of larger targeted therapies.
- Ado-trastuzumab emtansine (TDM1) shows potential for treating HER2-positive BCBM, warranting further clinical investigation.
- Further research is needed to establish treatment guidelines for this growing patient population.
