UAB O’Neal Cancer Center Research by Erica Stringer-Reasor, M.D., Leads to Breakthrough Study on Treatment for Leptomeningeal Metastasis in HER2-Positive Breast Cancer

A newly published study in Nature Cancer highlights a promising advance in the treatment of one of the most challenging complications of breast cancer, leptomeningeal metastasis (LM). The multi-institutional phase 2 clinical trial included contributions from researchers at the UAB O’Neal Cancer Center, led by Erica Stringer-Reasor, M.D. Associate Professor of Medicine and Director of the O’Neal Breast Cancer Program.

The study evaluated a three-drug combination — tucatinib, trastuzumab, and capecitabine — in patients with HER2-positive metastatic breast cancer that had spread to the leptomeninges, the membranes surrounding the brain and spinal cord. Historically, patients with this condition face a very poor prognosis, with limited treatment options and survival often measured in just a few months.

Results from the trial demonstrated meaningful clinical improvement. Patients receiving the regimen experienced a median overall survival of approximately 10 months, more than double the historical benchmark of 4.4 months. Additionally, the therapy showed encouraging effects in delaying disease progression in the central nervous system and improving neurological symptoms in many participants.

Importantly, the study also confirmed that tucatinib can penetrate the cerebrospinal fluid at therapeutic levels, a critical factor in treating cancers that spread to the central nervous system. The treatment combination was generally well tolerated, with a manageable safety profile, further supporting its potential as a new standard approach for this patient population.

The research was conducted in collaboration with leading cancer centers across the United States, including UAB, underscoring the importance of multi-site clinical trials in advancing cancer care. As a contributing investigator, Stringer-Reasor and her colleagues at UAB played a key role in designing the trial, enrolling patients, and analyzing data. 

While the findings represent a significant step forward, researchers note that additional studies are needed to refine treatment strategies, explore combinations with other therapies, and identify biomarkers that may predict which patients will benefit most.

This study marks an important milestone in improving outcomes for patients with HER2-positive breast cancer and leptomeningeal metastasis offering new hope where few effective options previously existed.