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

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

Astrocytoma is an extremely challenging diagnosis for both patients and doctors, as the variety of treatments and effectiveness are limited. “It is incredibly rewarding to participate in a study like STELLAR, which demonstrated a combination treatment that has significant benefit and offers incredible potential for patients with this specific diagnosis.”

Howard Colman, MD, PhD, co-director of the Huntsman Cancer Institute’s Neurological Cancers Disease Center, Jon M. Huntsman Presidential Professor in the U’s Department of Neurosurgery, and principal investigator of the STELLAR trial.

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

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

Initially, the study 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-mutated astrocytoma, and grade 4 IDH-mutated astrocytoma.

Astrocytomas are primary brain tumors that can form in the brain or spine. IDH, a mutated gene thought to drive the conversion of normal brain cells 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 groups. There was also no benefit from eflornithine in patients with astrocytomas or glioblastoma with grade 4 IDH mutation.

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

Colman and his team also considered each group’s progression-free survival rates, which measure how long it takes a patient’s disease to worsen after starting treatment. For patients with grade 4 IDH-mutated astrocytoma or glioblastoma, there was no significant improvement. But, similar to overall survival rates, patients with grade 3 IDH-mutated astrocytoma who received 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 double, 15.8 months.

“This is a groundbreaking advance. Advances in the treatment of brain tumors are critical to overcoming this difficult diagnosis for patients at Huntsman Cancer Institute and for patients across the country,” said 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 of cancer research in the U.S. Department of Population Health Sciences. “With each advance in the treatment of astrocytoma, we move closer to transform uncertainty into hope.”

This clinical trial is supported by the National Institutes of Health/National Cancer Institute, including Cancer Center Support Grant P30 CA042014, as well as the Huntsman Cancer Foundation.

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