New drug combination boosts life expectancy from grade 3 brain tumors by 45% or more

A new international study has delivered a rare dose of good news in the fight against aggressive brain tumors. Researchers found that a drug combination helped adults with recurrent grade 3 astrocytoma live longer and stay healthier for more time.

The findings come from the STELLAR clinical trial, a Phase 3 study that included patients from 74 hospitals and clinics across North America and Europe. Huntsman Cancer Institute at the University of Utah played a central role in the work.

A recurrent astrocytoma is one of the hardest diagnoses a patient can face. Treatment options are limited, and even when therapies work for a while, the cancer often returns. Grade 3 astrocytomas involving mutations in the IDH gene are especially challenging. This gene is thought to help push healthy cells toward becoming tumor cells, and once a tumor comes back, available therapies rarely add much time.

“Astrocytoma is an extremely challenging diagnosis for both patients and physicians, as the range of treatments and efficacy is limited,” said Howard Colman, MD, PhD, the study’s primary investigator at Huntsman Cancer Institute. His team joined dozens of others to test whether adding a newer drug, eflornithine, to the oral chemotherapy lomustine could help people survive longer.

Eflornithine works by blocking an enzyme that helps cancer cells grow. Lomustine is a long-standing chemotherapy used for several types of brain cancer. Researchers hoped that pairing the two would slow tumor progression more effectively than lomustine alone.

The STELLAR trial enrolled 343 adults whose brain tumors had returned after radiation and chemotherapy. As medical definitions evolved during the study period, the trial ultimately included patients with three types of tumors: grade 3 IDH-mutant astrocytoma, grade 4 IDH-mutant astrocytoma, and glioblastoma. Glioblastoma, the most common and aggressive of the three, usually lacks the IDH mutation and behaves differently.

Participants were randomly assigned to receive either the combination of eflornithine and lomustine or lomustine alone. Researchers measured two major outcomes. One was overall survival, or how long people lived after starting treatment. The second was progression-free survival, or how long it took for their disease to worsen.

When researchers looked at all patients together, the results were disappointing. The combination therapy did not increase overall survival across the full group. There was also no benefit for people with grade 4 IDH-mutant astrocytoma or glioblastoma. These cancers remained stubbornly resistant.

The turning point came when scientists focused on one subgroup: patients with recurrent grade 3 IDH-mutant astrocytoma. For them, the difference was meaningful.

The median overall survival was about 35 months on the combination therapy, compared with roughly 24 months on lomustine alone. That nearly one-year (45%) increase in survival is considered a significant improvement for this cancer type.

Progression-free survival showed an even stronger effect. Patients on lomustine alone had a median of 7.2 months before their disease worsened. Those taking the combination reached 15.8 months — more than double.

For families and care teams who often face limited choices at recurrence, this extended period without progression offers time that can be deeply important.

The findings provide a rare moment of optimism in a field where advances are slow and losses are common. “This is incredibly rewarding,” Colman said, noting the lack of effective options for patients with this recurring disease. The trial showed that pairing a newer drug with lomustine can move the needle for the right group of patients.

Neli Ulrich, PhD, MS, chief scientific officer at Huntsman Cancer Institute, said the results highlight the value of coordinated research efforts. “With every breakthrough in the treatment of astrocytoma, we move closer to transforming uncertainty into hope,” she said.

For many families, even one extra year can mean more chances to work, to connect, to wait for other treatments under development, or simply to live without constant medical setbacks. These gains can reshape the daily experience of a disease that often leaves few clear paths forward.

"However, not all patients benefited. Among those with IDH–wild-type disease, overall survival was nearly identical between the two arms, and progression-free survival was actually shorter in the combination group (3.4 months versus 6.8 months). A likely factor is that the lomustine dose in the combination arm had to be lowered to manage side effects, which may have reduced the drug’s impact in this faster-growing, more resistant tumor type," Ulrich explained to The Brighter Side of News.

"Even when all IDH-mutant tumors were grouped together regardless of CDKN2A/B status, the benefit of eflornithine appeared weaker than in the carefully defined IDH-mutant grade 3 subgroup. This supports the idea that the biological differences captured in the new WHO classification matter in real-world treatment decisions," he continued.

The combination therapy is not a cure, and it will not help all patients with recurrent brain cancer. It also will not improve outcomes for those with glioblastoma or grade 4 IDH-mutant astrocytoma. More research is needed to refine treatment strategies for those groups, which remain the most difficult to treat.

But for patients with recurrent grade 3 IDH-mutant astrocytoma, the STELLAR trial points to a new treatment direction — one that may soon influence how doctors treat this cancer when it comes back. The study shows that careful pairing of therapies can deliver meaningful gains, even when options appear limited.

The STELLAR trial offers real hope for one group of patients who face a devastating diagnosis. By doubling progression-free survival and extending overall survival by nearly a year, the combination of eflornithine and lomustine demonstrates that targeted drug pairings can meaningfully slow tumor growth.

These findings may guide future clinical practice, shift treatment standards for recurrent grade 3 IDH-mutant astrocytoma, and inspire new research into combination approaches for other aggressive brain cancers.

The work also shows the power of large, multi-center trials in bringing new options to patients who urgently need them.

Research findings are available online in the Journal of Clinical Oncology.

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