The antibody-drug conjugate sacituzumab govitecan-hziy may be effective in treating patients with breast cancer who have brain metastases or recurrent glioblastoma multiforme, according to a recent study published by Balinda et al in Nature Communications.
Background
About 50% of all female patients with aggressive and advanced triple-negative breast cancer may be diagnosed with brain metastases, the prognosis of which is often poor. These patients may experience a median overall survival of just over 7 months.
Brain tumors originating from breast cancer are common, and treatment of these tumors typically involves surgery, radiotherapy, and systemic therapies. However, these therapies are often unsuccessful. Similarly, glioblastoma multiforme is the most common type of primary brain malignancy in adults, representing approximately 50% of these tumors. It also is the most aggressive primary brain tumor, with a median survival of just 20.9 months, even following surgery, radiotherapy, chemotherapy, and tumor-treating regimens. As a result, there has been an unmet need to address breast cancer with brain metastasis and recurrent glioblastoma multiforme.
“We knew that [sacituzumab govitecan] has been effective in the treatment of breast cancer, but its usefulness in [the] treatment of resulting brain tumors has been unclear,” explained senior study author Andrew J. Brenner, MD, PhD, Professor and Chair of Neuro-Oncology Research at the Mays Cancer Center as well as Co-Leader of the Experimental and Development Therapeutics Program and a clinical investigator at the Institute for Drug Development at The University of Texas Health Science Center at San Antonio (UT Health San Antonio). “Our trial, however, revealed that it could achieve concentrations of inhibitors inside the tumors sufficient to benefit patients, and with minimal side effects, which is very promising for new therapy,” he added.
Study Methods and Results
In the recent prospective window-of-opportunity trial, researchers assigned 25 patients (aged 18 years or older) who had been diagnosed with breast cancer and brain metastases or recurrent glioblastoma multiforme to receive a single intravenous dose of sacituzumab govitecan 1 day prior to tumor-tissue removal and on days 1 and 8 of 21-day cycles following recovery. The time frames were 8 months for patients with breast cancer who had brain metastases and 2 months for those with recurrent glioblastoma multiforme.
The researchers found that sacituzumab govitecan was well tolerated and showed signs of effectiveness in the patients whose breast cancer had progressed to brain tumors. They observed significant penetration of the topoisomerase inhibitor SN-38 inside the tumors that received the drug—and without unexpected adverse effects.
Conclusions
“[Sacituzumab govitecan] could achieve intratumoral concentrations of SN-38 sufficient for therapeutic benefit in patients with brain metastases from breast cancer and recurrent glioblastoma [multiforme]. The drug was well tolerated in this population with promising clinical signals of efficacy,” underscored the study authors.
The researchers indicated that their findings may support ongoing investigation of sacituzumab govitecan in patients with recurrent glioblastoma multiforme in a phase II clinical trial.
“We currently are in the interim analysis stage of that phase II trial, which enrolled 20 patients at UT Health San Antonio, Cleveland Clinic, and Texas Oncology in Austin,” detailed co–study author William Kelly, MD, Assistant Professor of Hematology and Oncology at the Mays Cancer Center at UT Health San Antonio. “We expect it will shed further light on the possible effectiveness of [sacituzumab govitecan] in treating glioblastoma [multiforme],” he concluded.
Disclosure: For full disclosures of the study authors, visit nature.com.
