New combination treatment helps people with recurring grade 3 astrocytoma, trial shows

Huntsman Cancer Institute at the University of Utah (the U) participated in a clinical trial that found that a new combination treatment plan helped people with recurring grade 3 astrocytoma, an aggressive form of brain cancer, live longer.

Astrocytoma is an extremely challenging diagnosis for both patients and physicians, as the range of treatments and efficacy is limited. It's incredibly rewarding to be involved in a study like STELLAR, which demonstrated a combination treatment that has a significant benefit and offers incredible potential for patients with this specific diagnosis."

Howard Colman, MD, PhD, co-leader of the Neurologic Cancers Disease Center at Huntsman Cancer Institute, Jon M. Huntsman Presidential Professor in the Department of Neurosurgery at the U, and primary investigator of the STELLAR trial

The Phase 3 trial from Orbus Therapeutics evaluated the efficacy and safety of a treatment plan using a combination of the drug eflornithine, a compound that targets an enzyme to inhibit the proliferation of tumor cells, and the oral chemotherapy lomustine, which is used to treat a variety of brain cancers.

The international trial enrolled 343 patients from 74 hospitals and clinics in North America and Europe, including Huntsman Cancer Institute. All patients had to have previously received radiation and chemotherapy, as well as had recurrence of the disease after treatment.

The study initially enrolled patients who had a type of brain tumor called anaplastic astrocytoma. But as medical definitions changed, the study ended up including three types of brain tumors: glioblastoma, grade 3 IDH-mutant astrocytoma, and grade 4 IDH-mutant astrocytoma.

Astrocytomas are primary brain tumors that can form in the brain or spine. IDH, a gene that mutates and is thought to drive the conversion of normal cells in the brain into tumor cells, is the most common driver of astrocytoma tumors. Glioblastoma is a different type of astrocytoma that is more aggressive and does not involve mutations in the IDH gene.

In the STELLAR trial, the experimental group of patients received oral eflornithine in combination with lomustine. The other half, the control group, received lomustine alone.

Among all patients, the study found no difference in overall survival rates between the control and experimental group. There was also no benefit of eflornithine for patients with grade 4 IDH-mutant astrocytomas or glioblastoma.

But for patients with grade 3 IDH-mutant astrocytoma, the new treatment helped them live much longer-about 35 months compared to 24 months with the standard treatment.

Colman and his team also considered the progression-free survival rates of each group, which measure how long it takes for a patient's disease to worsen after starting treatment. For patients with grade 4 IDH-mutant astrocytoma or glioblastoma, there was no significant improvement. But, as in overall survival rates, patients with grade 3 IDH-mutant astrocytoma on the combination therapy fared better. Patients taking lomustine alone had a median progression-free survival rate of 7.2 months. In patients taking the combination therapy of lomustine and eflornithine, the median was more than twice as long, at 15.8 months.

"This is a groundbreaking development. Advances in treating brain tumors are critical to overcoming this difficult diagnosis for Huntsman Cancer Institute's patients and patients throughout the country," says Neli Ulrich, PhD, MS, chief scientific officer and executive director of the Comprehensive Cancer Center at Huntsman Cancer Institute and Jon M. and Karen Huntsman Presidential Professor in Cancer Research in the Department of Population Health Sciences at the U. "With every breakthrough in the treatment of astrocytoma, we move closer to transforming uncertainty into hope. Through federally funded cancer research and strong public–private partnerships, we are accelerating scientific discovery and bringing new, powerful treatments to the patients who need them most."

This clinical trial is supported by the National Institutes of Health/National Cancer Institute, including cancer center support grant P30 CA042014, as well as Huntsman Cancer Foundation.

The results of the study were published in the Journal of Clinical Oncology.