Investigational Drug May Combat Brain Tumors By Targeting Cancer Cells' Fat Production
The oral drug is currently being evaluated in phase I clinical trials for Parkinson’s disease.
Press Release5 Minute ReadOct | 20 | 2021
Priscilla K. Brastianos, MDThis is an exciting first step towards showing that immune checkpoint blockade may have a role in treating this devastating disease.
BOSTON – Two new studies indicate that immunotherapy may benefit people with leptomeningeal carcinomatosis (LMD), a rare but serious complication of cancer that has spread to the brain and/or spinal cord. The research, which was led by investigators at Massachusetts General Hospital (MGH), Dana-Farber Cancer Institute and the Broad Institute, is published in Nature Communications.
Although advances in cancer treatment have extended patient survival, some cancers come back, often in a different location in the body. This may in part help explain recent increases in the incidence of LMD—when tumor cells infiltrate the leptomeninges (layers of tissue that cover the brain and spinal cord) and cerebrospinal fluid. Approximately 5–8% of all patients with cancer develop LMD after first being diagnosed with breast cancer, lung cancer, melanoma or other malignancies. Current treatment options rarely benefit patients with LMD, and there is an urgent need for new therapies.
Immune checkpoint inhibitors are important medications that boost the immune system’s response against various cancers, but their effects against LMD are unclear. To investigate, researchers conducted two phase II clinical trials. When they collected and analyzed immune cells and cancer cells from the cerebrospinal fluid of patients in the trials both before and after treatment with immune checkpoint inhibitors, the scientists found signs that the therapy was having an effect. For example, the number of certain cancer-killing immune cells and the expression of particular genes within cells were higher following treatment.
The second article in Nature Communications presents the results of one of the phase II studies, which included 18 patients with LMD who received combined ipilimumab and nivolumab (two types of immune checkpoint inhibitors) until the cancer progressed or the patient experienced unacceptable toxicity. The primary endpoint was overall survival at 3 months, and 8 of the 18 patients were alive at that time. (Historically, patients survive for a median of 3–7 weeks after being diagnosed with LMD.) One-third of patients experienced one or more serious adverse events. Two patients discontinued treatment due to unacceptable toxicity. The most frequent adverse events include fatigue, nausea, fever, anorexia and rash.
The authors noted that larger, multicenter clinical trials are needed to validate their results.
“In these two published studies, we demonstrated—in patients through a clinical trial and microscopically in the laboratory—that immune checkpoint blockade has promising activity for patients with LMD. More data is needed, but this is an exciting first step towards showing that immune checkpoint blockade may have a role in treating this devastating disease,” says co-author Priscilla K. Brastianos, MD, who is the director of the Central Nervous System Metastasis Center at MGH and an associate professor of medicine at Harvard Medical School.
Funding for the trial was provided by Bristol Myers Squibb and MGH.
About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2021, Mass General was named #5 in the U.S. News & World Report list of "America’s Best Hospitals."
The oral drug is currently being evaluated in phase I clinical trials for Parkinson’s disease.
The new agent, called TB-403, was well tolerated and induced stabilization of the disease in some medulloblastoma patients.
A collaborative project to bring the promise of cell therapy to patients with a deadly form of brain cancer has shown dramatic results among the first patients to receive the novel treatment.
Mass General Cancer Center’s precision medicine approach resulted in 91 percent reduction in tumor size, with all 15 patients who received one or more cycles of therapy responding to treatment.
In a phase 2 trial of patients with brain cancer that metastasized from a wide range of primary tumors, Mass General Cancer Center researchers found that the immune checkpoint inhibitor pembrolizumab had a durable, antitumor effect in a subset of patients.
Taking losartan might allow patients with brain cancer to continue receiving immune checkpoint inhibitors without experiencing the medications’ potentially deadly side effect.
The oral drug is currently being evaluated in phase I clinical trials for Parkinson’s disease.
The new agent, called TB-403, was well tolerated and induced stabilization of the disease in some medulloblastoma patients.
A collaborative project to bring the promise of cell therapy to patients with a deadly form of brain cancer has shown dramatic results among the first patients to receive the novel treatment.
Mass General Cancer Center’s precision medicine approach resulted in 91 percent reduction in tumor size, with all 15 patients who received one or more cycles of therapy responding to treatment.