HER2+ Breast Cancer: New Hope for Leptomeningeal Metastases Treatment
A combination of targeted therapies and chemotherapy has shown promising results in extending survival and improving symptoms for women with advanced breast cancer that has spread to the brain, according to a new study from The University of Texas MD Anderson Cancer Center.
The Phase II trial, published today in Nature Cancer, focused on patients with HER2-positive breast cancer and leptomeningeal metastasis (LM) – a rare and aggressive form of cancer spread where tumor cells disseminate into the cerebrospinal fluid and coat the membranes surrounding the brain and spinal cord. Historically, LM has been associated with a poor prognosis and limited treatment options.
Researchers evaluated a regimen of tucatinib, trastuzumab, and capecitabine in 17 women newly diagnosed with LM. The median overall survival increased to 10 months, a significant improvement compared to the historical average of 4.4 months, according to the study. At the 18-month mark, 41% of patients were still alive.
“The combination achieved a clinically meaningful improvement in overall survival compared to historical controls,” said Rashmi Murthy, M.D., associate professor of Breast Medical Oncology at MD Anderson and lead author of the study. “For these patients, who often face limited treatment options, our results represent a step forward, offering new hope in how we treat and manage leptomeningeal metastasis.”
The study also indicated improvements in neurological symptoms. Seven of 12 patients evaluated experienced improved neurological deficits, and the median time to central nervous system progression was seven months. Five of 13 patients showed an objective response to the treatment in terms of LM.
Tucatinib, a targeted therapy, was found to reach therapeutic levels in the cerebrospinal fluid, a key factor in its potential effectiveness against LM. The treatment combination was generally considered safe and tolerable, with manageable side effects including diarrhea, nausea, vomiting, hand-foot syndrome, and elevated liver enzymes.
Barbara O’Brien, M.D., professor of neuro-oncology and co-author of the study, noted that previous treatments for LM have largely focused on stabilization of the disease rather than symptom improvement. “In addition to the encouraging results on survival, throughout the study we observed improvements in neurological symptoms,” she said.
The trial was a non-randomized, single-arm study, and researchers acknowledged limitations including a unhurried recruitment rate and the small sample size due to the rarity of the condition. Further research is needed to confirm these findings and explore the potential of this treatment combination in a larger patient population. ClinicalTrials.gov registration: NCT03501979.