Combo treatment may offer new hope to astrocytoma patients: Trial
New data show improved survival when adding eflornithine to chemotherapy
Treatment with the experimental medication eflornithine in combination with the approved chemotherapy Gleostine (lomustine) may help improve survival in people with aggressive astrocytoma carrying IDH mutations.
That’s according to newly published results from a Phase 3 clinical trial, which showed — using new criteria — that median survival for participants given the combination treatment was nearly three years. That compared with a median survival of nearly two years for patients with this aggressive glioma who did not receive eflornithine along with chemotherapy, per the researchers’ analysis.
“The positive results … represent a true breakthrough as the first treatment to show this magnitude of benefit compared to the standard of care in this fatal tumor type, and a major step forward for patients,” Howard Colman, MD, PhD, of the Huntsman Cancer Institute at the University of Utah, said in a press release from Orbus Therapeutics, the company developing eflornithine.
In announcing the findings, Orbus noted that the “eflornithine and lomustine combination doubled progression free survival (PFS) and improved overall survival (OS) in patients with recurrent [returning after treatment] … astrocytoma.”
The findings from the trial were detailed in “STELLAR: Phase III, Randomized, Open-Label Study of Eflornithine Plus Lomustine Versus Lomustine Alone in Patients With Recurrent Grade 3 Astrocytoma,” a paper published in the Journal of Clinical Oncology. The work was funded by Orbus.
Astrocytoma is a form of glioma caused by the uncontrolled growth of star-shaped brain cells that support nerve function. Like other cancers, astrocytomas can be classified into different grades, with higher grades, such as grade 3, reflecting a more aggressive form of the disease. Treatments such as chemotherapy and radiation can help reduce cancer growth, but in many patients, the cancer will grow back, or recur.
“Grade 3 astrocytoma is an aggressive malignant glioma that is challenging to treat despite radiation and chemotherapy. When it recurs, as it does in most cases, patients are faced with limited treatment options and a very poor prognosis,” Colman said.
STELLAR trial tested combo treatment in over 300 astrocytoma patients
Eflornithine is a compound that reduces cell growth by blocking the activity of ornithine decarboxylase, an enzyme that’s present at elevated levels in certain cancers. It is approved in the U.S. under the name Iwilfin as a maintenance therapy to reduce the risk of recurrence in people with high-risk neuroblastoma, another type of brain cancer that occurs due to the abnormal growth of immature nerve cells.
The Phase 3 STELLAR clinical trial (NCT02796261), which was launched in 2016, enrolled 343 people with astrocytoma that had recurred following first-line treatment with chemotherapy or radiation. To be eligible for the study, patients had to have grade 3 cancer, as defined by 2016 guidelines from the World Health Organization (WHO).
The participants were randomly assigned to take eflornithine in addition to Gleostine or the chemotherapy only. The main goal was to see if the addition of eflornithine would improve survival outcomes.
To our knowledge, this magnitude of improvement demonstrated with the eflornithine/[Gleostine] combination compared to standard of care has not been seen in this patient population.
Initial analyses from the overall trial population showed no difference in survival outcomes between patients who received or did not receive eflornithine.
However, there was a notable wrinkle in the trial’s analysis: In 2021, the WHO updated its criteria for grading astrocytoma, and based on the new criteria, nearly half of the patients in STELLAR would have been classified as grade 4 instead of grade 3.
To account for this update, the researchers conducted preplanned analyses examining outcomes in 196 patients with grade 3 cancer according to the new criteria. All of these patients had tumors carrying mutations in IDH, a protein that is frequently mutated in gliomas. In this subset of patients, the median time to disease progression was more than eight months longer in patients given elfornithine (15.8 v 7.2 months), the new analysis showed.
Moreover, median survival was nearly a year longer — 34.9 versus 23.5 months.
“To our knowledge, this magnitude of improvement demonstrated with the eflornithine/[Gleostine] combination compared to standard of care has not been seen in this patient population,” said Jason Levin, president and CEO of Orbus.
Orbus now planning to discuss findings with regulatory authorities
Safety data from the trial were consistent with the known profiles of eflornithine and Gleostine. The most common serious side effects included low immune cell counts, which were reported in more than 40% of patients given the combination treatment, and hearing impairment, which was reported in approximately 1 in 4 patients given eflornithine.
Levin said that Orbus is planning to consult with regulatory authorities on the next steps for developing eflornithine in astrocytoma.
“The publication in JCO underscores the strength of the data, which we hope will provide a meaningful advancement for patients facing this devastating disease who have had no new chemotherapy options in over two decades,” Levin said.
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